HandbookOfOpthalmology

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HYPHEMA

SIGNS AND SYMPTOMS

Patients may present with blurred vision, pain, photophobia and tearing following blunt, concussive injury to the eye or orbit. Hyphemas (blood in the anterior chamber) are described by the amount of anterior chamber (AC) they occupy:

Grade 1 = less than one-quarter of the visible volume of the AC Grade 2 = one-quarter to one-half of the visible volume of the AC Grade 3 = one-half to three-quarters of the visible volume of the AC Grade 4 = complete filling of the visible AC

The term "eight-ball hemorrhage" is reserved for completely filled anterior chambers with black-colored clots.

PATHOPHYSIOLOGY

There are two suggested mechanisms of hyphema formation. Either direct, contusive forces cause mechanical tearing of the fragile blood vasculature of the iris and/or angle, or concussive trauma creates rapidly rising intravascular pressure within these vessels, resulting in rupture.

Blood in the AC is not by itself necessarily harmful. However if quantities are sufficient it may obstruct the outflow of aqueous humor, resulting in glaucoma. Hemolytic glaucoma results from direct obstruction of the trabecular meshwork by fresh blood. Hemosiderosic glaucoma results from trabecular meshwork obstruction from degrading hemoglobin. Ghost cell glaucoma results from trabecular meshwork obstruction by the skeletons of the disintegrating red blood cells. Finally, any external force strong enough to produce internal bleeding is also sufficiently strong to produce direct damage to the adjacent trabecular meshwork, resulting in sluggish aqueous drainage (late glaucoma).

MANAGEMENT

A thorough history is critical. Circumstances surrounding the event, current medicines and previous ocular history are important pieces of data. Bleeding in the eye warrants questioning concerning systemic blood disorders such as sickle cell anemia, hemophilia and Von Willebrand's disease (vascular hemophilia). If the patient is a poor historian or questions arise regarding systemic health, order systemic tests for sickle cell anemia (sickle prep or sickle dex) and bleeding disorders (PT and PTT).

Ocular examination should include an evaluation of the adnexa (X-ray, CT scan to rule out fracture or entrapment) cornea (to rule out perforation), sclera (to rule out ruptured globe), anterior chamber, lens, vitreous and retina. If a clear view of the fundus is obstructed by the hyphema or vitreous hemorrhage, perform or refer for a B-scan ultrasound of the globe.

Whether these individuals should be hospitalized is controversial. Most practitioners manage

uncomplicated hyphemas (grade 1) without hospital admission. Cycloplege the patient with atropine 1% BID/QID and prescribe a steroid such as Pred Forte or Vexol Q2H/QID. If intraocular pressure is above 27mm Hg, it should be controlled using topical beta-blockers BID. When IOP requires acute attention (i.e., over 35mm Hg) prescribe acetazolamide 500mg PO BID, barring systemic contraindications, until the pressure is adequately controlled. If there are corneal epithelial defects, Rx a topical antibiotic

prophylactically. Instruct the patient to limit activity to the bathroom and bed rest, laying with the head elevated at an angle of 30 degrees. Provide an eye shield for additional protection.

To prevent re-bleeding, use only acetaminophen to manage pain; avoid aspirin and ibuprofen. Referral for surgical evaluation is indicated if there is corneal blood staining, if IOP is greater than 60mm Hg, if there is

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an eight-ball hemorrhage or if the IOP remains above 35 for seven days. Follow up with VA, slit lamp, IOP and dilated fundus exam for four consecutive days, then as necessary.

CLINICAL PEARLS

Gonioscopy is contraindicated because it increases the risk of re-bleeding. However, up to 50 percent of patients with hyphema possess angle recession and the possibility of developing a secondary traumatic late glaucoma. Monitor the IOP of these patients regularly. The onset of secondary glaucoma is between 12 months and 50 years. Perform gonioscopy after the event has resolved and the risk of re-bleeding has passed.

• Aminocaproic acid (Amicar 50mg/kg), an antifibrinolytic, has been advocated by some to reduce the risk of re-bleeding. One of its potential side effects is severe nausea and vomiting, a

contraindication in patients with hyphema. The medicine seems to function best in children but is not universally accepted and remains controversial.

PRIMARY OPEN ANGLE GLAUCOMA (POAG)

SIGNS AND SYMPTOMS

Although early POAG patients are virtually asymptomatic, there are at least three definitive signs: elevated intraocular pressure

(approximately 21mm Hg or more), enlargement of the optic cup and repeatable field loss. Other possible signs include nerve fiber layer dropout, notching of the neuroretinal rim at the inferior or superior poles, and splinter hemorrhages adjacent to the optic disc.

PATHOPHYSIOLOGY

Despite decades of research and over two million diagnosed cases of open angle glaucoma in the U.S. alone, much remains unknown about this disease. Elevated intraocular pressure almost certainly plays a significant role, but the process is poorly understood. According to the mechanical theory of POAG, chronically elevated IOP crimps the axons of retinal ganglion cells as they pass through the lamina cribrosa, eventually killing the cells. The vascular theory suggests that, with elevated IOP, reduced blood flow to the optic nerve starves the cells of oxygen and nutrients.

New research presented in 1996 offers another possible mechanism of ganglion cell death. Studies show that some glaucoma patients exhibit elevated levels of the neurotransmitter glutamate within the vitreous. Ganglion cells contain protein receptors that, when activated by glutamate, increase intracellular calcium to toxic levels, killing the cells.

MANAGEMENT

Although several new IOP lowering drugs have been released in the past few years, beta-blockers continue to be the mainstay of glaucoma therapy. The typical management plan is to set a target IOP at least 25 percent below pre-treatment levels, and prescribe your beta-blocker of choice two or three times per day until the target is reached.

The 19-year-old timolol (Timoptic) is the most commonly prescribed beta-blocker available, but others are also noteworthy. Betimol from Ciba Vision Ophthalmics is a new, low-cost formulation of timolol that, unlike Timoptic, cannot be surreptitiously replaced with a generic by the pharmacist.

A familiar but often overlooked beta-blocker that is gaining in prominence is betaxolol (Betoptic). This drug selectively blocks beta-1 receptors, largely sparing beta-2 receptors in the lungs and thereby making it

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a safer option for patients with some pulmonary conditions. Betoptic also has less likelihood of reducing blood flow (and may, in fact, increase perfusion) to the optic nerve than other beta-blockers, has less propensity to reduce the levels of HDL cholesterol in blood, and preserves the visual field equally or better than other beta-blockers, even though its IOP reduction tends to be somewhat less. Finally, new research also shows that betaxolol provides ganglion cells with at least some protection from calcium toxicity caused by glutamate binding.

Other unique beta-blockers include carteolol, which, like betaxolol, has less propensity to reduce HDL cholesterol levels, and Timoptic-XE, which allows for once-a-day therapy.

New medications such as the prostaglandin analog latanoprost (Xalatan) and the topical carbonic anhydrase inhibitor dorzolamide (Trusopt) offer alternative therapies, but beta-blockers have been the gold standard against which all new pressure lowering medications are measured, and this is unlikely to change. In all likelihood, beta-blockers will remain the first-line therapy of choice in POAG, and prostaglandin analogs will supplant older second-line therapies. Xalatan is comparable in IOP lowering effect to Timoptic; its main side effect is darkening of the pigment in light-colored irises.

Another new IOP lowering drug, the alpha-2 adrenergic agonist brimonidine (Alphagan), has not been proven clinically superior to apraclonidine (Iopidine) although it is approved for chronic use whereas Iopidine 1% is intended to control post-surgical pressure spikes and angle closure attacks. A lower concentration, Iopidine 0.5%, has been developed and approved for chronic care of POAG patients. It is likely that Alphagan and Iopidine will equally share the alpha-2 adrenergic agonist market.

CLINICAL PEARLS

Prostaglandin analogs reduce IOP by increasing aqueous outflow through the uveoscleral pathway by dilating the spaces between ciliary muscle bundles. However, miotics such as pilocarpine tighten these bundles by contracting the iris dilator muscle, so these two medications are counter-effective. Discontinue any miotics prior to adding Xalatan to the regimen.

To improve compliance for patients on multiple medications, it is helpful to identify the cap colors of each drug being used (e.g., "Remember to use the one with the yellow cap twice a day and the blue one four times a day.")

ACUTE ANGLE CLOSURE GLAUCOMA

SIGNS AND SYMPTOMS

Patients with angle closure glaucoma manifest symptoms of ocular and facial pain, unilateral blurring of vision, photopsiae in the form of colored haloes around lights, and occasionally nausea and vomiting. Acuity may be reduced significantly in the involved eye, often to 20/80 or worse.

The hallmark signs of angle closure include significantly elevated intraocular pressure, a closed angle upon gonioscopic evaluation, deep conjunctival and episcleral injection in a circumlimbal fashion, and a fixed, mid-dilated pupil. Upon slit-lamp examination, you may also see an edematous or "steamy" cornea and shallow anterior chamber.

Applanation tonometry may reveal IOP in the range of 30 to 60mm Hg, or even higher in some cases. Gonioscopy, which may prove difficult because of microcystic corneal edema, reveals no visible angle structures without indentation. There may be evidence of previous angle closure episodes in the form of peripheral anterior synechiae (PAS) in the fellow eye.

PATHOPHYSIOLOGY

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endothelium and impedes aqueous outflow. Several mechanisms are possible. The most common etiology of angle closure is pupillary block, whereby the flow of aqueous from the posterior to anterior chamber is inhibited, causing iris bombé. This may be simply due to genetic predisposition and anterior segment anatomy (primary pupil block), or from posterior synechiae, lenticular enlargement or displacement of the lens or IOL (secondary pupil block).

Another mechanism which may induce angle closure involves an abnormal configuration of the iris, the so-called "plateau iris syndrome." Patients with this presentation may boast a deep anterior chamber centrally; however, the iris demonstrates an unusual laxity, coming into close approximation with the angle

peripherally. These patients may be prone to "angle crowding" and subsequent closure during physiologic or pharmacologic dilation. Other etiologies of angle closure without pupil block include neovascular membranes inducing PAS, anterior uveal displacement (such as in choroidal detachment) or, rarely, posterior segment inflammation or tumors.

MANAGEMENT

The paramount concern in managing an angle closure attack is to lower IOP quickly. Your choice of primary medication depends upon the pressure at presentation. As most miotics are ineffective at pressures over 40mm Hg due to iris ischemia, immediately treat such patients with a beta-blocker of 0.5%

concentration and/or apraclonidine 1%.

Next, perform corneal compression with a gonioprism to aid in lowering the IOP by forcing aqueous into the trabeculum and temporarily opening the angle. It may be necessary to use topical glycerin to clear the cornea if there is significant edema. Perform tonometry every 15 minutes after initiating therapy.

If the patient does not achieve significant reduction in IOP after 45 minutes, administer an oral carbonic anhydrase inhibitor (acetazolamide 2 x 250mg tablets). You may also wish to use a hyperosmotic agent such as three to five ounces of oral glycerin or isosorbide over ice. Once the IOP is below 40mm Hg, instill pilocarpine 2% as well as prednisolone acetate 1% every 15 minutes to abate the attack and reopen the angle. It is safe to discontinue this regimen when the IOP is below 30mm Hg and the angle structures are again visible with gonioscopy. Maintain the patient on the following medications: pilocarpine 2% QID, prednisolone acetate 1% QID, timolol (or equivalent) 0.5% BID, and oral acetazolamide 500mg BID.

When the inflammation has diminished and the AC is quiet, refer the patient for a peripheral iridotomy. This provides a secondary outflow channel for aqueous, and commonly causes a permanent anatomical "deepening" of the anterior chamber.

CLINICAL PEARLS

• The most important consideration in handling an acute angle closure attack is accurate diagnosis and prompt intervention. First distinguish between angle closure glaucoma and other acute open angle conditions such as uveitic glaucoma, glaucomatocyclitic crisis and phacolytic glaucoma. Once you have established angle closure as the cause, you must also differentiate the nature of the attack, whether due to primary pupillary block, plateau iris, or secondary pupillary block. If you are uncertain of the etiology or if an inflammatory glaucoma is present, do not use a miotic, as this will only exacerbate the condition.

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SIGNS AND SYMPTOMS

The typical presentation of anterior uveitis involves pain, photophobia and excessive tearing. Patients report a deep, dull aching of the involved eye and surrounding orbit. Associated sensitivity to lights may be severe; often, these patients will present wearing dark sunglasses. The excessive tearing occurs secondary to increased neural stimulation of the lacrimal gland, and is not associated with a foreign body sensation.

Visual acuity is not usually impaired to any great extent (20/40 or better is common), although patients may report some haziness. Accommodative tasks, however, may prove more difficult and uncomfortable. Inspection may reveal mild to moderate congestion of the lids, resulting in pseudoptosis. You'll typically see a deep perilimbal injection of the conjunctiva and episclera, although the palpebral conjunctiva is characteristically normal. The cornea may display mild edema upon biomicroscopy. In more severe reactions, you may observe grayish brown endothelial deposits, known as keratic precipitates.

The hallmark signs of anterior uveitis are "cells and flare." Cells are leukocytes (white blood cells) floating in the convection currents of the aqueous; flare refers to liberated protein from the inflamed iris or ciliary body which gives the aqueous a particulate, or smoky, appearance. The iris may adhere to the lens capsule (posterior synechia) or, less commonly, to the peripheral cornea (anterior synechia). Additionally, you may see granulomatous nodules within the iris stroma.

Intraocular pressure in the affected eye is initially reduced due to secretory hypotony of the ciliary body. However, as the reaction persists, inflammatory by-products may accumulate in the trabeculum. If this debris builds significantly, and if the ciliary body resumes its normal secretory output, the pressure may rise sharply, resulting in a secondary uveitic glaucoma.

PATHOPHYSIOLOGY

Uveitis, as the name implies, represents an inflammation of the uveal tissues, chiefly the iris and ciliary body. Inflammation may be associated with underlying systemic disease, or it may occur as a direct result of ocular trauma. Occasionally, inflammatory reactions in adjacent tissues (e.g., keratitis), can induce a secondary uveitis.

Uveitis can be either acute or chronic. The chronic form is more often associated with systemic disorders including, but not limited to, ankylosing spondylitis, Behçet's syndrome, inflammatory bowel disease, juvenile rheumatoid arthritis, Reiter's syndrome, sarcoidosis, syphilis, tuberculosis, and Lyme disease. Chronic uveitis most likely occurs due to an immunopathological mechanism which is not fully understood.

MANAGEMENT

There are two primary goals when managing anterior uveitis. First, immobilize the iris and ciliary body to decrease pain and prevent exacerbation of the condition. Second, quell the inflammatory response. Begin by cyclopleging the patient with homatropine 5% TID/QID, scopolamine 0.25% BID/QID or atropine 1% BID, depending upon the severity of the reaction. Next, prescribe a topical steroid Q2-3H, or more often if the reaction is severe. If there's a posterior synechia present, attempt to break the adhesion in the office using atropine 1% and phenylephrine 10%. Treat secondary elevations in IOP using standard anti-glaucoma agents, such as timolol 0.5% BID or dorzolamide 2% TID.

Avoid pilocarpine in uveitic glaucoma, as it will only serve to worsen the inflammatory response by mobilizing the uveal tissues. After beginning treatment, re-evaluate the patient every one to seven days depending on the severity of the reaction. As the uveitis resolves, discontinue the cycloplegics and taper the steroids to QID or TID. Generally, it is better to taper slowly rather than abruptly, and patients may need to remain on steroid drops daily or every other day for several weeks. In recalcitrant uveitis which is

unresponsive to conventional therapy, consider injectible steroids such as methylprednisolone 60mg or even oral steroids such as prednisone 60 to 80mg.

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CLINICAL PEARLS

• Acute anterior uveitis results most commonly as a result of blunt ocular trauma. In most instances, these cases resolve without incident and do not recur when properly managed.

• Consider any cases of recurrent uveitis, defined as three or more unexplained incidents, to be representative of underlying systemic inflammatory disease until proven otherwise. Hematologic testing is indicated for any recurrent, chronic or bilateral presentation. A standard battery of laboratory tests should include: complete blood count (CBC) with differential, antinuclear antibody (ANA), HLA-B27, rheumatoid factor (RF), angiotensin-converting enzyme (ACE), purified protein derivative (PPD), fluorescent treponemal antibody absorption (FTA-ABS) and rapid plasma reagin (RPR). A chest X-ray is also important in identifying both sarcoidosis and tuberculosis. A Lyme titer is also recommended if you suspect that the patient may have been bitten by a deer tick.

• Always perform a comprehensive, dilated fundus evaluation in these cases. Anterior uveitis may actually constitute a "spillover" of posterior ocular inflammation.

LENS INDUCED GLAUCOMAS

SIGNS AND SYMPTOMS

The lens induced glaucoma patient is typically elderly, with a history of cataracts. There are four types of glaucomas associated with lens complications (excluding cases of lens displacement in ectopia lentis):

• phacolytic glaucoma

• lens particle glaucoma

• phacoanaphylactic uveitis

• phacomorphic glaucoma

In all of these cases, the glaucoma is typically very symptomatic with pain and redness in the involved eye, and cells and flare in the anterior chamber. Frequently, an advanced cataract in the involved eye severely reduces vision.

PATHOPHYSIOLOGY

Phacolytic glaucoma This condition involves a hypermature cataract with severe visual reduction (typically light perception). It's characterized by acute onset of pain and redness and IOPs often of 35mm Hg or greater. There is liquefaction of the lens nucleus and cortex, and attenuation of the capsule with the release of lens proteins into the anterior chamber. Macrophages engulf the lens proteins, become bloated, and block trabecular outflow. The angle remains open, though in some cases peripheral anterior synechiae may develop.

Lens particle glaucoma The mechanism of lens particle glaucoma resembles that of phacolytic glaucoma,

except that there is a history of surgery or trauma that releases the lens proteins into the anterior chamber and initiates a macrophage-driven inflammatory reaction. The angle remains open.

Phacoanaphylactic uveitis This is a chronic uveitis that occurs one to 14 days following cataract

extraction or lens trauma. This mechanism is similar to the previous two types of glaucoma, except that inflammatory cells are not limited to macrophages. Also, there is considerable flare and mutton-fat keratic precipitates, and a propensity for synechiae formation. The angle may be open or closed.

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Phacomorphic glaucoma In this case, an increase of lens thickness from an advancing cataract leads to a

relative pupil block, posterior bombé and angle closure. The intumescence often develops quickly. Typically, the cataract reduces vision severely. The angle in this glaucoma is closed.

MANAGEMENT

Employ topical beta blockers, carbonic anhydrase inhibitors and alpha adrenergic agonists to temporize the IOP. Avoid miotics and prostaglandin analogs in cases where inflammation is present. In cases where there is significant anterior segment inflammation, use topical steroids to quell the inflammation. In cases where the lens precipitates a secondary glaucoma, the best management is surgical lens removal.

CLINICAL PEARLS

• In cases of severe granulomatous uveitis with IOP rise following cataract extraction, consider phacoanaphylactic uveitis.

• In patients with hypermature cataracts and shallow anterior chambers with angle closure, consider phacomorphic glaucoma, especially if the fellow lens has less intumescence and there is a deeper chamber.

• Phacomorphic and phacolytic glaucoma develop only in eyes with hypermature cataracts. Vision typically ranges from 20/400 to light perception. If vision is better than 20/400, consider another cause for the glaucoma.

• In cases where there is phacomorphic glaucoma in a nanophthalmic eye, surgical excision of the cataract is associated with severe complications of choroidal detachment and hemorrhage. In these cases, you may prefer medical therapy and laser iridotomy rather than surgical management.

PSEUDOEXFOLIATION SYNDROME AND

PSEUDOEXFOLIATIVE GLAUCOMA

SIGNS AND SYMPTOMS

Patients with pseudoexfoliation syndrome remain asymptomatic until an advanced glaucoma develops. The condition is most common in the sixth to eighth decade, with actual glaucoma developing later in this age range. There is no racial, sexual or geographic predilection. Typically, pseudoexfoliation syndrome begins unilaterally, but becomes bilateral within about seven years.

The patient presents with a fine, flaky material on the anterior lens capsule at the pupillary margin. Over time, this coalesces into a characteristic "bulls-eye" pattern seen in pseudoexfoliation. There is often increased transillumination of the iris at the pupillary margin and there may be pigment granules on the endothelium and iris surface. Within the angle, there may be observable pigment or clear flaky material. Initially, intraocular pressure is unaffected; however, elevated IOP develops in up to 80 percent of patients. In these cases, glaucomatous cupping and visual field loss may ensue.

PATHOPHYSIOLOGY

Due to accumulation of abnormal basement membrane material at the pupillary margin, there is increased apposition with the iris and subsequent erosion of iris pigment as the pupil dilates and constricts. This leads to increased iris transillumination and deposition of pigment granules on the endothelium, iris surface and trabecular meshwork similar to pigment dispersion syndrome. Because this condition involves deposition of material on the anterior lens capsule, and not flaking-off of the lens capsule, lensectomy is not a remedy. In fact, some have observed exfoliative material deposits on intraocular lens implants.

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The development of glaucoma typically occurs due to a buildup within the trabecular meshwork of pigment granules and pseudoexfoliative material. Patients develop a secondary open angle glaucoma. However, studies have identified patients with increased IOP but no decrease in aqueous outflow. In these cases, the glaucomatous mechanism is unknown.

MANAGEMENT

Pseudoexfoliation syndrome without a pressure rise requires only periodic monitoring of IOPs, discs and visual fields. When first diagnosing pseudoexfoliation syndrome, perform automated visual fields to look for preexisting field loss since pseudoexfoliative glaucoma undergoes periods of exacerbation and remission.

Treat pseudoexfoliative glaucoma in the same manner as primary open angle glaucoma. Use topical beta-blockers, topical carbonic anhydrase inhibitors, prostaglandin analogs and alpha adrenergic agonists if not systemically contraindicated. However, the IOP level in pseudoexfoliative glaucoma is typically higher than in POAG and is more difficult to temporize. Laser trabeculoplasty and filtration surgery are often employed earlier than in POAG.

CLINICAL PEARLS

• An initially normal IOP measurement does not preclude prior IOP elevation with subsequent field loss and disc damage. Remember that pseudoexfoliative glaucoma undergoes periods of

exacerbation and remission. Serial photographs and automated visual fields are more appropriate for managing this condition than IOP measurements, since the patient may experience progression yet manifest normal IOP if measured during remission.

• Argon laser trabeculoplasty and filtration surgery are more effective in controlling IOP in cases of pseudoexfoliative syndrome than in POAG.

Neovascular Glaucoma

Signs and Symptoms

Patients with neovascular glaucoma (NVG) may be asymptomatic, but more typically present with a chronically red, painful eye which often has significant vision loss. Further, there will be significant concurrent vascular disease such as diabetes, hypertension, carotid artery disease, or giant cell arteritis (GCA). There frequently is an antecedent history of a retinal vessel occlusion or chronic uveitis. There will be visible neovascularization of the iris (NVI) and angle (NVA). Only rarely will NVA develop without NVI. The patient typically has significant corneal edema and elevated intraocular pressure, often exceeding 50-mm-Hg. There may be a shallow anterior chamber. Gonioscopically, there will be total or near-total angle closure. Funduscopically, there typically will be evidence of retinal vessel occlusion (either artery or vein), ocular ischemic syndrome or diabetic retinopathy.

Pathophysiology

Ischemia to ocular tissues is theorized to be the genesis of NVG. The most common causes of NVG include ischemic central retinal vein occlusion (CRVO), diabetic retinopathy, and carotid artery disease and ocular ischemic syndrome (OIS). Less common causes of NVG include hemi- and branch retinal vein occlusion, retinal artery occlusion, and GCA. In terms of retinal vein occlusions, NVG typically develops within three

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months of the occlusion. In terms of retinal artery occlusions, NVG typically develops within four weeks of the occlusion.

In ischemic retinal disease, hypoxia induces vascular endothelial growth factor (VEGF), a vasoproliferative substance, with acts upon healthy endothelial cells of viable capillaries to stimulate the formation of a fragile new plexus of vessels (neovascularization). In cases of extreme retinal hypoxia, there are essentially very few viable retinal capillaries available. In that instance, VEGF is theorized to diffuse forward to the nearest area of viable capillaries, namely the posterior iris. Neovascularization buds off of the capillaries of the posterior iris, grows along the posterior iris, through the pupil, along the anterior surface of the iris, and then into the angle. Once in the angle, the neovascularization, along with its attendant fibrovascular support membrane, acts to both physically block the angle as well as bridge the angle and physically pull the iris and cornea into apposition, thus blocking the trabecular meshwork. Peripheral anterior synechiae with permanent angle closure happens quickly. The result is a secondary angle closure without pupil block. Due to the extremely elevated intraocular pressure, there will be a modest amount of inflammation.

Management

If there is any degree of inflammation and ocular pain, prescribe a topical cycloplegic such as atropine 1% b.i.d. as well as a topical steroid such as Pred Forte, Vexol, or Flarex q.i.d. Aqueous suppressants may be used in order to temporarily reduce IOP. However, chronic medical therapy is not indicated for neovascular glaucoma. Aqueous suppressants will temporize IOP and lead to a false sense of security as the neovascular process will continue with further angle closure.

Ultimate management of NVG involves eradication of the vessels. This is best accomplished with pan-retinal photocoagulation to destroy ischemic retina, minimize oxygen demand of the eye, and reduce the amount of VEGF being released. PRP tends to be effective in causing regression and involution of anterior segment neovascularization. If a significant amount of the angle is in permanent synechial closure, filtering surgery must then be employed.

Clinical Pearls

• PRP has a 90 percent success rate in NVG due to diabetes if less than 270º of the angle is closed. However, if NVG is due to ocular ischemic syndrome, PRP is less successful and 90 percent of these patients will have count fingers vision within one year.

• In cases of NVG in elderly patients, always consider GCA as a potential etiology.

• Retinal artery occlusions develop NVG in only 17 percent of cases and typically within four weeks post-occlusion.

• Miotics are absolutely contraindicated in any case where there is active inflammation. Prostaglandin analogs should likewise be avoided.

BACTERIAL KERATITIS

Signs and Symptoms

The patient with bacterial keratitis will generally present with a unilateral, acutely painful, photophobic, intensely injected eye. Visual acuity is usually

reduced, and profuse tearing is common. There will be a focal stromal infiltrate with an overlying area of epithelial excavation. Often, there will be a history of contact lens wear, which is the most common

Culture-proven Pseudomonas keratitis with mucopurulent discharge.

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precipitating condition. Corneal trauma or pre-existing keratopathy are also common precipitating conditions.1

Mucopurulent discharge may emanate from the lesion. The cornea may be edematous. The conjunctival and episcleral vessels will be deeply engorged and inflamed, often greatly out of proportion to the size of the corneal defect. In bacterial keratitis, injection is typically 360 degrees rather than sectoral as seen in non-infectious keratitis. A pronounced anterior chamber reaction, often with hypopyon, is present in severe cases. Intraocular pressure may be reduced due to secretory hypotony of the ciliary body, but may be elevated due to blockage of the trabecular meshwork by the inflammatory cells. Often, the eyelids will also be edematous.

Pathophysiology

Once the corneal defenses are breached, the cornea is prone to colonization and infection by pathogenic bacteria. Factors known to compromise corneal defenses include direct corneal trauma, chronic eyelid disease, systemic immune disease, tear film abnormalities affecting the ocular surface and hypoxic trauma from contact lens wear.2

Pathogenic bacteria colonize the corneal stroma and immediately become antigenic, both directly and indirectly, by releasing enzymes and toxins. This sets up an antigen-antibody immune reaction with chemotactic factors inducing an inflammatory reaction. The body mobilizes polymorphonuclear leukocytes (PMN), which aggregate at the area of infection, creating an infiltrate. The PMNs phagocytize and digest the bacteria and damage stromal tissue by releasing numerous enzymes that directly affect and damage stromal tissue.

The collagen of the corneal stroma is poorly tolerant of the bacterial and leukocytic enzymes, and undergoes degradation, necrosis and thinning. This leads to scarring of the cornea. As thinning advances, the cornea may perforate, thus introducing bacteria into the eye with ensuing endophthalmitis.

The most commonly occurring organisms in bacterial keratitis vary depending on the precipitating factors of the ulcer and the geographic location of the patient. In cases involving contact lens wear and cosmetic mascara, the most common infective organism is Pseudo-monas aeruginosa. Throughout North America, the most common infective organism in bacterial keratitis is

Staphylococcus aureus, and it appears that there is an increased incidence of Gram-positive recovery in infectious keratitis.3

Management

Proper diagnosis and prompt therapy are essential to preserve vision in bacterial keratitis. The first step in management should be to obtain corneal scrapings for microbiologic studies. The standard of care describes the use of a platinum spatula with plating directly onto blood and chocolate agar medium. However, the effectiveness of the fluoroquinolones has led many practitioners away from this standard. Identification, as well as sensitivity studies, will aid in management. An alternative for treatment of less severe keratitis is a mini-tip calcium alginate culturette and transport-media-containing carrier. The results of this technique compared to platinum spatula collection and plating was 83.3% sensitivity and 100% specificity. The conservative approach supports culturing most, if not all, suspected infectious ulcers. We advocate obtaining cultures for central lesions that threaten vision, are at risk of perforation, and in institutionalized patients in nursing homes and hospitals where methicillin-resistant Staph. aureus infections are possible.4

If the patient has been cultured, initiate broad-spectrum, empirical antibiotic therapy prior to receiving the results. Monotherapy with fluoroquinolone eye drops has been shown to result in

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shorter duration of intensive therapy and shorter hospital stay when compared with combined fortified therapy (tobramycin-cefazolin). This finding may have resulted from quicker clinical response of healing as a result of less toxicity found in the patients treated with fluoroquinolones. However, as some serious complications were encountered more commonly in the

fluoroquinolone group, caution should be exercised in using fluoroquinolones in large, deep ulcers in the elderly.5

Despite clear efficacy of fluoroquinolones in the management of bacterial keratitis,2,6-8

consideration must be given to the increasing resistance to these drugs. Since their inception, there has been a rise in the incidence of bacterial isolates in keratitis that exhibit resistance to the early generation fluoroquinolones.2,3,9 One method of combating the increasing problem of

fluoroquinolone resistance and rising level of Gram-positive infections is to use the new fourth-generation topical fluoroquinolones.

Traditional initial monotherapy has utilized the fluoroquinolone Ciloxan (ciprofloxacin, Alcon), two drops every 15 minutes for six hours, followed by two drops every 30 minutes for 18 hours, and then tapered depending on patient response. Another second-generation fluoroquinolone, Ocuflox (ofloxacin, Allergan), is also an effective treatment for bacterial keratitis.7 Both

fluoroquinolones have been proven to be as effective for managing bacterial keratitis as the previously used fortified antibiotics, but with significantly fewer side effects. Unfortunately, bacterial resistance to the second-generation fluoroquinolones has been increasing, especially among the Gram-positive organisms. The two most recently available fourth-generation fluoroquinolones, moxifloxacin (Vigamox, Alcon) and gatifloxacin (Zymar, Allergan), have a greatly lowered resistance rate while providing much greater Gram-positive activity than previous generation fluoroquinolones.10 In the future, Zymar or Vigamox dosed on an hourly basis may

become the mainstay therapy for bacterial keratitis.

Strong cycloplegia is also mandatory in order to increase patient comfort and minimize

inflammation. The weakest cycloplegic that should be employed is scopolamine 0.25% tid. If this is insufficient, then atropine 1% bid is indicated. Adjunctive use of cold compresses will also help to reduce inflammation.

The patient should be followed daily until the infection is well controlled. If the results of cultures and sensitivities show that the initially prescribed antibiotic is appropriate for the infective organism, or if the patient shows signs of clinical improvement (the ulcer does not worsen, and pain and photophobia are reduced) at the 24 to 48 hour follow-up visit, a topical corticosteroid such as prednisolone acetate 1% or loteprednol etabonate 0.5% q2h can be added to speed resolution and decrease corneal scarring.

While steroids have historically been avoided in the management of infectious keratitis, judicious use can be beneficial. Antibiotics can suppress the infective organism, while corticosteroids can inhibit the corneotoxic inflammatory response. It has been feared that the immunosuppressive effects of steroids could enhance bacterial replication and worsen infection. However, if the chosen antibiotic is effective against the organism, then the concurrent use of steroids will not inhibit the bactericidal effect of the antibiotic.1117 But note that steroids should not be employed

until the antibiotic has been given enough time to sterilize the ulcer, minimally 24 hours. One also must be certain that there is not a simplex viral, fungal, or protozoan infection prior to the initiation of topical steroids. Also, steroids should only be used in conjunction with true bactericidal

antibiotics such as fluoroquinolones.

Clinical Pearls

• If a patient presents with a corneal infiltrate without overlying epithelial staining, then the condition may not be infectious bacterial keratitis.

(12)

• The use of strong bactericidal antibiotics will eliminate the infective organisms and sterilize the ulcer, but will do nothing to quell the inflammatory reaction. In this instance, the inflammatory reaction is as damaging to the cornea as is the infective organism. If there is evidence that the antibiotic is suppressing the infective organism, then corticosteroid use will inhibit the inflammatory reaction and speed healing and reduce corneal scarring.

• For steroids to be most beneficial, prescribe them while the ulcer bed is still open, usually within the first 24 to 48 hours after you initiate antibiotic therapy. If you wait until the ulcer re-epithelializes before adding a steroid, the beneficial effects will be reduced. A

cautionary note: Be comfortable that the antibiotic has sterilized the ulcer before instituting the steroid.

PANNUS

Definition: The word "pannus" takes its origin from the Latin meaning "a piece

of cloth." Relating to the eye, it is pathologically defined as a superficial vascularization of the cornea with infiltration of inflammatory-connective-granulation tissue. Pannus is not a diagnosis; it is a finding that results secondary to another disease process.111

Diseases associated with pannus

• LASIK2

• Allergic conjunctivitis3,11

• Toxic conjunctivitis3

• Neonatal conjunctivitis3

• Chlamydial conjunctivitis3,11

• Fuch's endothelial dystrophy4,5

• Congenital hereditary endothelial dystrophy6

• Superior limbic keratoconjunctivitis of Theodore7

• Terriens marginal degeneration7

• Mycobacterial tuberculos pannus8

• Leprosy8

• Aniridia9

• Keratoconjunctivitis10

Immune Stromal (Interstitial) Keratitis

Signs and Symptoms

Patients with active immune stromal keratitis (ISK) will present with pain, photophobia, lacrimation, and blepharospasm. Vision is typically reduced in the acute, active phase. The presentation may be either unilateral or bilateral. There will often be a history of ocular infection or systemic disease. However, ISK may be the initial manifestation of an unknown

Pannus lesion.

(13)

underlying systemic disease. Occasionally, ISK is idiopathic. ISK runs a chronic, indolent course and may persist for many months.

There will be a single or multiple white patches of infiltration and inflammation within the corneal stroma. There will be concurrent stromal edema as well as stromal vascularization. Typically, the overlying epithelium is intact. If there is epithelial disruption, it will be much smaller in area than the underlying inflammation. Corneal thinning may result as sequelae of the chronic inflammation; however, thinning is not a distinctive feature. There will be a secondary anterior uveitis.

Endothelial folds and keratic precipitates are common.

Pathophysiology

ISK is an immune-mediated nonsuppurative stromal inflammation with an intact epithelium. ISK is typically associated with an often readily identifiable causative agent. Conditions causing SK include Epstein Barr virus, herpes zoster and simplex, mumps, measles, Lyme disease, Acanthamoeba infection, tuberculosis, syphilis, sarcoidosis and onchocerciasis. However, the most common cause of active ISK is the herpes simplex virus, accounting for over 70% of unilateral active cases.1 Sixty percent of cases of bilateral, active ISK are idiopathic in nature.

Syphilis is the cause of approximately 50% of bilateral inactive cases. Although syphilis is the leading cause of inactive, bilateral ISK, it is actually responsible for less than 20% of total cases.1

It must be emphasized that there is no active microbial infection within the corneal stroma in ISK. Rather, microbial antigens initiate a T-lymphocytic destruction of the stroma.2 Subsequent stromal

vascularization and cicatrization invariably results if the underlying cause is left untreated. The stromal vascularization will begin during the acute phase and progress throughout the disease's course. However, the presence of stromal vascularization is not required in order to make this diagnosis (as was previously thought).

There are two types of ISK that may occur during herpes simplex infections: necrotizing and non-necrotizing. Necrotizing herpetic ISK is a more severe form of herpetic stromal keratitis and manifests as a dense, cheesy, yellow-white stromal infiltration often following recurrent herpetic disease. There will be epithelial ulceration, stromal edema, dense vascularization, profound corneal thinning, and possible perforation. Non-necrotizing herpetic ISK does not have the same propensity to move toward ulceration, thinning, and perforation. Untreated, non-necrotizing ISK runs an indolent, self-limiting course over several months. Fortunately, the majority of herpetic ISK cases are non-necrotizing.

Management

Immune stromal keratitis is a self-limiting condition, which will spontaneously resolve within several months. However, the result invariably will be profound stromal vascularization and scarring with subsequent visual reduction. Hence, treatment is indicated. It must be remembered that ISK is an immune stromal keratitis and not an active infectious process. Application of a strong steroid such as prednisolone acetate 1% q1h to q2h is optimal. Depending upon the etiology, the patient may need to use low doses of topical steroids indefinitely. Cycloplegia and topical lubrication will ease the patient's discomfort.

When ISK is caused by the herpes virus, therapy deviates somewhat from the above-mentioned regimen. Lower doses of topical steroids may be employed to control the patients' disease and symptoms. When topical steroids are used to treat herpetic immune stromal disease, prophylactic topical antiviral medications (trifluridine) should be used concurrently.3,4 There has been no

proven benefit for the adjunctive use of oral acyclovir in the acute management of patients with herpes simplex stromal keratitis being treated with topical corticosteroids and trifluridine.5

(14)

Herpes simplex ISK is a highly recurrent disease, with the risk related to the number of previous recurrences.6 Long-term suppressive oral therapy with acyclovir 400mg po bid has been shown to

significantly reduce the recurrence rate of not only epithelial keratitis from herpes simplex, but also stromal disease.7,8 Strong consideration should be given for long-term suppressive therapy

beyond one year in herpes simplex stromal keratitis.

As ISK can result from a variety of causes, a diagnostic evaluation should be initiated. Unless the cause is obviously herpetic, medical evaluation for IK should include FTA-ABS or MHA-TP for syphilis, PPD and chest X-ray for tuberculosis, Lyme titer for Lyme disease, and rheumatoid factor and antinuclear antibodies for collagen vascular disease. Should a cause be elicited, the patient should receive medical treatment directed toward the underlying cause while he or she undergoes topical treatment.

Particular attention must be paid to patients presenting with ISK and hearing loss, signaling Cogan's syndrome. Cogan's syndrome is an idiopathic inflammatory disease, which may present as ISK, inflammation of other ocular structures, Meniere's-like attacks, audiovestibular

dysfunction or systemic vasculitis. Although the ocular manifestations respond to topical steroids and are rarely serious, permanent deafness may result if systemic steroid therapy is not promptly instituted for audiovestibular dysfunction, while major morbidity and even death may occur if systemic sequelae such as vasculitis and aortic insufficiency are not recognized.9

Clinical Pearls

• If a patient develops ISK on the same side as a prior episode of either HSV or HZV and there is no indication of other disease in the patient's history, then no further diagnostic evaluation is necessary. In this case, it can safely be assumed that the cause of the ISK is herpetic.

• Historically, ISK has been associated with syphilis as the main causative agent. Today, however, syphilis is the main cause only in cases of bilateral, inactive ISK. By far, the main identifiable cause of active cases of ISK is herpes simplex virus.

• In cases of active herpetic ISK, topical and oral antiviral medications have been

exceedingly disappointing therapeutically. The only use for either oral or topical antiviral medications in herpetic IK is prophylactically to prevent epithelial ulceration when topical corticosteroids are used and to suppress future recurrences.

• Stromal inflammatory infiltration in herpetic ISK can be difficult to differentiate from both bacterial and fungal keratitis. However, IK will have a more intact epithelium whereas the other entities will have ulceration. Further, IK runs an indolent course, whereas infectious keratitis is much more aggressive.

• As in other herpetic manifestations, corneal sensitivity is reduced on the affected side.

• Suspect Cogan's syndrome in patients presenting with ocular inflammation who develop hearing loss, vertigo, ataxia, tinnitus, vasculitis, or aortic insufficiency.

DRY EYE SYNDROME

Signs and Symptoms

Dry eye syndrome may occur in a wide range of individuals, although it is more frequently seen in women, the elderly, and those with connective tissue disorders (e.g., rheumatoid arthritis, Sjögren's syndrome). Patients with dry eye commonly present with complaints of ocular irritation or discomfort. As

Generalized injection associated with moderate dry eye.

(15)

the name implies, dryness is the most frequently cited problem; patients may further report itching, burning, or a "sandy/gritty" foreign body sensation. Symptoms may be exacerbated by poor air quality, low humidity or extreme heat, and tend to be more prominent later in the day. Occasionally, patients will report excess lacrimation, or epiphora, in association with the discomfort.

Upon gross inspection, the majority of these patients demonstrate a relatively white and quiet eye. However, key slit lamp findings may include a meager tear meniscus at the lower lid, as well as a reduced tear break-up time (TBUT), generally less than ten seconds. Sodium fluorescein staining may be evident as punctate epithelial keratopathy from the interpalpebral region to the lower third of the cornea. In more severe cases, rose bengal or lissamine green staining of the cornea and/or conjunctiva may be seen in the same area. Filaments, which are tags composed of mucus, epithelial cells and tear debris, may also stain with these vital dyes.

Additional clinical tests for dry eye syndrome are numerous. Tear volume assessment is used quite commonly, and may be ascertained by use of Schirmer tear test strips or the Zone-Quick test. Dimin-ished "wetting" of these test media over a set period of time (five minutes for the Schirmer and 15 seconds for the Zone-Quick test) is indicative of tear volume deficiency, a form of dry eye syndrome. Another device, the Keeler Tearscope, utilizes interferometry to evaluate the thickness of the tear film components, particularly the lipid layer. More involved and invasive procedures, including tear film osmolarity, lysozyme analysis, lactoferrin assay, and impression cytology, may be useful in quantifying dry eye for research purposes, but they are hardly practical for routine clinical diagnosis.

Pathophysiology

Dry eye syndrome has traditionally been viewed as a quantitative or qualitative reduction in the precorneal tear film, with a multitude of etiologies and

contributory factors. The condition tends to be categorized as either "tear deficient" or "evaporative," based upon a comprehensive classification scheme that was developed in 1995.1 Those conditions that

contribute to diminished tear production, such as Sjögren's syndrome or lacrimal gland disease, constitute the tear- deficient variety. Conditions

involving mucin or lipid deficiencies (e.g., Stevens-Johnson syndrome or blepharitis), irregular ocular surface topography, altered blink reflex, or other surface disorders comprise evaporative dry eye. Other contributory factors may include contact lenses, low environmental humidity, and high altitude.

Over the last several years, a great deal of research has been conducted in the area of dry eye, revealing startling new information. Of the more intriguing theories is that dry eye may be the result of an inflammatory process within the cornea and/or lacrimal glands.24 This is supported by

the fact that pro-inflammatory cytokines and activated T cells have been identified in the lacrimal glands of both Sjögren's and non-Sjögren's patients.5,6 In addition, moderate to severe dry eye

states have been seen to respond favorably to treatment with corticosteroids.7 On another front,

researchers have shown a significant link between androgens and dry eye.8,9 Apparently, these

sex hormones may help regulate homeostasis of the tear secretion process. Women who take hormone replacement therapy with estrogen have an increased incidence of dry eye, possibly due to suppression of endogenous androgens by increased estrogen levels.10,11

Management

Negative corneal staining from surface disease in dry eye.

(16)

Historically, management of dry eye syndrome has been aimed at replenishing the eye's moisture and/or delaying evaporation of the patient's natural tears. The first line of defense typically

involves the use of ophthalmic lubricants ("artificial tears"). The purpose of these agents is to alleviate symptoms and, in some cases, to promote healing of the ocular surface epithelium. A great deal of diversity exists within this market, and practitioners should familiarize themselves with the various options (see "Overview of New Dry Eye Products," on page 34A). In general, artificial tears may be used as frequently as necessary, although some are only indicated for qid use. When beginning therapy, they should be dosed frequently (at least every hour), and then tapered based upon patient response and compliance.

Patients who do not respond to palliative therapy may require more substantial treatment in the form of topical and/or oral pharmaceutical agents. The immunomodulatory agent Restasis (0.05% cyclosporine A ophthalmic emulsion, Allergan) has recently been approved by the U.S. FDA "for patients with keratoconjunctivitis sicca ... whose tear production is presumed to be suppressed due to ocular inflammation." Although this topical drug may require bid dosing for up to six months to achieve maximum efficacy, it has been shown to ameliorate symptoms in up to 44% of patients and improve basal tear production (as demonstrated by Schirmer testing) in up to 59% of patients.12

Oral medications and nutritional supplements have been utilized with success for patients with blepharitis and meibomian gland disease, significant causes of evaporative dry eye syndrome. The use of oral tetracycline therapy (e.g., doxycycline 100mg bid x six to 12 weeks) may be beneficial in patients who fail to improve with lubricating drops and lid hygiene. Also, the use of oral omega-3 fatty acid supplements has been suggested as a less invasive way to improve meibomian gland function and tear stability.13

Lacrimal occlusion with punctal or intracanalicular plugs offers a different management strategy for dry eye, essentially preventing drainage of the tear film and maximizing contact duration with the ocular surface. While the theory is sound, a significant percentage of plugs may be

spontaneously expelled, and it has been noted that many patients notice a subjective decrease in improvement of symptoms with the plugs over time.14,15 Some individuals have actually cautioned

against occlusion therapy in many cases, citing the new inflammatory theories of dry eye; they suggest that the use of punctal plugs actually creates a "cesspool" of cytokines and promotes, rather than alleviates, damage to the ocular surface.16

Patients with keratoconjunctivitis sicca (KCS), a more severe form of dry eye, may not respond to any topical therapy. Often, these patients benefit from oral secretagogues such as Salagen (pilocarpine HCl 5 mg, MGI Pharma) and Evoxac (cevimeline HCl 30 mg, SnowBrand

Pharmaceuticals). These muscarinic agonists stimulate non-selective secretion from exocrine glands via autonomic pathways, resulting in enhanced tear production. Typically these agents are used for xerostomia (dry mouth) associated with Sjögren's syndrome or certain forms of cancer. They are utilized by some physicians for advanced KCS; however this is not currently an FDA-approved application of these drugs.

Clinical Pearls

• The symptoms of dry eye syndrome tend to be quite variable. Often, patients seem to be more symptomatic than their clinical signs would indicate. Astute clinicians realize that the diagnosis of dry eye is more often based on subjective complaints than on ocular inspection.

• Many common systemic drugs can transiently decrease lacrimal secretions, creating or exacerbating a dry eye state. These may include antihistamines, oral contraceptives, beta-blockers, diuretics, phenothiazine antianxiety preparations, many antidepressants and atropine derivatives.

(17)

• Before initiating any form of therapy, practitioner and patient alike must understand one basic tenet of dry eye management: namely, that this is a chronic disease, marked by exacerbations and remissions. The only way for patients to achieve control of their symptoms and discomfort is through active participation in the prescribed treatment regimen and periodic reevaluation. There is no "magic bullet" cure, and appropriate care requires patience, perseverance and a willingness to try new (and sometimes

unconventional) options.

CORNEAL ABRASION

Signs and Symptoms

Corneal abrasion is one of the common clinical entities that present to the optometric practice. Patients usually present with some or all of the following: acute pain, photophobia, lacrimation, bleph-arospasm, foreign-body sensation, blurry vision and a history of contact lens wear or being struck in the eye.111

Biomicroscopy of the injured area often reveals diffuse corneal edema and epithelial disruption. In severe cases, when edema is excessive, folds in Descemet's membrane may be visible. Cobalt blue light inspection, following the instillation of sodium fluorescein dye, will illuminate the denuded epithelium. The newly created wound appears as a bright green area compared to the rest of the cornea because the dye accumulates in the divot, adding

density.3,5,10

Pathophysiology

The cornea has five distinct layers. Below the tears lies the corneal epithelium. The corneal epithelium is actually composed of three tissues: the stratified surface epithelium, the wing cell layer, containing the corneal nerves and the mitotically active basement membrane. Below the epithelium is the Bowman's membrane (a structure designed to prevent penetrating injuries), 250 lamellar sheets of stroma, Descemet's membrane, and finally the endothelium.

There are two categories of corneal abrasion; superficial, not involving Bowman's membrane and deep, penetrating Bowman's membrane, but not rupturing Descemet's membrane. Abrasions may result from foreign bodies, contact lenses, chemicals, fingernails, hair brushes, tree branches, dust and the like.

The cornea has remarkable healing properties. The epithelium adjacent to any insult expands in size to fill in the defect, usually within 24 to 48 hours.5 Lesions that are purely epithelial often heal

quickly and completely without scarring. Lesions that extend below Bowman's membrane possess an increased risk for leaving a permanent opacity.5 Recent data suggests that the

integrity of the basement membrane following the injury is a deciding factor in determining the regenerative character of the corneal repair.7

For years contact lenses have remained at the top of the list of consumer goods known to perpetrate ocular injuries. Further, ulceration following contact lens-induced corneal abrasion has been recognized and demonstrated as a secondary phenomenon to suspect compliance, care and lens cleanliness.8 In one study, ulcers were found only in corneas that were scratched with

contact lenses colonized by viable S. aureus.8 Bacteriologic examination of lenses at the time of

the event demonstrated the association.8

Corneal abrasion without fluorescein.

(18)

Management

Treatment for corneal abrasion begins with history. The time, place and activity surrounding the injury should be recorded for both medical and legal purposes.

Visual acuity (VA) should be recorded before any procedures or drops are given, if possible. If the blepharo-spasm is sufficiently intense to preclude an acuity measurement, one drop of topical anesthetic from a recently open bottle can be administered. The VA should be measured immediately thereafter. The eye examination should proceed in a logical fashion from external adenexa to funduscopic examination. The eyelids should be everted and fornicies scrutinized to rule out the presence of foreign material. Fluorescein dye (without

anesthetic) should be instilled to identify the corneal defects. The Seidel test (painting of the wound with dye observing for aqueous leakage) is used to uncover full-thickness injuries. The abrasion should be documented for size, shape, location and depth. Any anterior chamber reaction should be observed and noted as well. A dilated examination should be completed to rule out posterior effects from the trauma.

Medical treatment is initiated by using adequate cycloplegia (the potency of which should be determined on a case-by-case basis) and topical antibiotics such as Polytrim (polymyxn B and trimethoprim, Allergan), gentamicin or Tobrex (tobramicin, Alcon) or a fluoroquinolone (Vigamox, Zymar). Bed rest, inactivity and over-the-counter analgesics can be used to quiet acute pain. In cases where pain is severe, topical nonsteroidal anti-inflammatory medications (Voltaren or Acular, qid) or a thin, low water content bandage contact lens can be prescribed.16, 9, 10, 11

Pressure patching is no longer considered standard-of-care.1,2,46,10 Researchers examined patients

with corneal abrasion: 17 with an eye patch and 18 with no eye patch. There was no significant difference in percent healing between the two groups, even when adjusted for age and initial abrasion size. Consistent with the data of others, pressure patching for corneal abrasions provides no benefit.10 Patching must always be avoided in patients who wear contact lenses due

to the threat of microbial keratitis. Patients should be reevaluated every 24 hours until the abrasion

is reepithelialized.15

Clinical Pearls

• To prevent recurrent erosion and reduce corneal edema, a hypertonic solution or ointment may be prescribed along with the other medications or after reepithelialization has occurred.5

• In cases where excess epithelium impairs regrowth, a cotton-tipped applicator saturated with anesthetic may be used to debride loose tissue.5

• When significant secondary uveitis is present, topical steroids may be required.

• Worsening subepithelial infiltration may be a sign of infection. Lesions such as these should be considered vision threatening, warranting immediate treatment with fluoroquinolone antibiotic drops and consideration for culture.3

OVERVIEW OF NEW DRY EYE PRODUCTS

FOR MANY YEARS, there were only two options for managing dry eye syndrome: either put more moisture into the eye, or prevent the moisture already present from evaporating too quickly. Ophthalmic lubricating solutions, more commonly known as artificial tears, have remained the mainstay of dry eye therapy since their introduction in the 1940s.1 Freeman introduced the first

silicone punctal plug in 1975,2 and other devices to prevent surface evaporation (e.g. Moist Eye

Corneal abrasion with fluorescein staining.

(19)

moisture panels from EagleVision) have joined the ranks over the years, but these modalities have never been able to supplant artificial tear therapy from its #1 position.

A cursory review of an online health product service (www.drugstore.com) reveals over 50 distinct items when the term "artificial tears" is entered in the search engine! With so many products to choose from, it can be frustrating and intimidating for both patients and practitioners to know which option to select. The following is a review of some of the more recent products introduced for therapy of dry eye syndrome.

Trends in Artificial Tears

Despite their popularity and success, two significant difficulties still exist with artificial tears. The biggest issue is duration of action; patients frequently report only fleeting relief (on the order of five to 10 minutes) after instillation of many tear supplements. Also of concern is the addition of preservatives in many artificial tears, which can be a significant source of toxicity, particularly when these preparations are used frequently. Therefore, manufacturers have begun producing thicker, more viscous agents that increase corneal contact time without blurring vision. Examples of such products include Refresh Liquigel (Allergan), GenTeal Gel (Novartis), TheraTears Liquid Gel (Advanced Vision Research), and Systane (Alcon). Also, manufacturers have introduced several preservative-free solutions and "disappearing preservatives" to address the issue of toxicity. Virtually every line of dry eye products includes a preservative-free version (e.g., Tears Naturale PF, Hypotears PF, etc.), but only three product lines contain preservatives that break down soon after instillation. These include: GenTeal (Novartis, preserved with GenAqua, or sodium perborate), Tears Again (Cynacon/Ocusoft, preserved with Dissipate), and Refresh Tears (Allergan, preserved with Purite).

Nature's Tears

In mid-2002, a small company based in Oregon launched a unique product that has captured the interest of many exhibit hall attendees. Nature's Tears (Bio-Logic Aqua Technologies) is

described by the manufacturer as an all natural moisturizing mist for the eyes consisting simply of tissue culture grade water with no preservatives or propellants. Rather than being instilled as a drop, Nature's Tears is sprayed toward the eyes from a distance of 12 to 18 inches. The premise? Artificial tears flood the ocular surface, washing away the lipid and mucin layers and depleting normal enzymes, claims the manufacturer. However, Nature's Tears mist allows for replenishing of the aqueous component without disturbing the other tear layers. This is an intriguing theory, and the product possesses a significant novelty factor. However, there is a lack of significant prospective studies demonstrating that this product is any more effective than other artificial tear supplements.

Endura

In the summer of 1999, the FDA Ophthalmic Drugs Subcommittee advisory panel unanimously recommended not to approve Allergan's formulation of topical cyclosporine for the treatment of keratoconjunctivitis sicca. One of the reasons cited was that the solution vehicle showed very similar efficacy to the drug itself, and hence there was no significant difference between the controls and the study group. Undaunted, Allergan decided to manufacture this unique vehicle, an emulsion of castor oil and lubricants in an aqueous solution, and market it directly to the public as an over-the-counter product. In the fall of 2002, Refresh Endura was launched.

According to Allergan, Endura is the first lubricant eye drop for dry eye that treats all three layers of the tear film. It is preservative-free and packaged in single-use, disposable vials. Controlled clinical trials with Endura showed enhanced fluorescein tear break-up time, as well as diminished symptoms of dryness and irritation in patients using the solution two to four times daily over 90

(20)

days. Clinical practice has shown it to be an excellent and well-tolerated solution, particularly suited for patients with lipid deficiencies secondary to meibomian gland dysfunction.

Systane

In early 2003, Alcon introduced a unique artificial tear product. Systane, which utilizes the demulcent technology of hydroxypropyl (HP) guar, increases in viscosity after contacting the ocular surface. This change is based on pH value. Systane is a liquid in the bottle at a pH of 7.0, but when placed in the eye (which has a pH of ~7.4), a chemical reaction occurs. HP guar binds to the ocular surface and simultaneously crosslinks with borate ions in the solution, forming a network with a gel-like consistency. The result is a more viscous ocular lubricant that, according to Alcon, provides extended relief of dry eye symptoms and generates a protective coating on the ocular surface. In theory, this coating serves as a temporary corneal bandage, allowing the epithelial cells to heal and reestablish healthy microvilli and a normal glycocalyx.

In a randomized, controlled clinical trial, dry eye patients receiving Systane four times daily for six weeks showed a statistically significant reduction in surface staining, dryness and foreign-body sensation, as well as increased tear break up time.3,4 Mild blurring for 30 seconds after instillation

was the most significant adverse effect. Personal experience with Systane has shown it to be an outstanding choice for patients with moderate to severe dry eye who are not ameliorated with normal viscosity tear solutions. It is also excellent for managing minor corneal trauma or exposure keratopathy.

Restasis

In December 2002, the FDA approved Restasis (0.05% cyclosporine ophthalmic emulsion) for the treatment of keratoconjunctivitis sicca, making it the first commercially available pharmaceutical therapeutic agent for the treatment of dry eye. This topical solution is classified as an

immunomodulatory agent by the manufacturer (Allergan), and is approved "for patients with keratoconjunctivitis sicca...whose tear production is presumed to be suppressed due to ocular inflammation."

In clinical studies, Restasis was shown to ameliorate symptoms in up to 44% of patients and improve basal tear production (as demonstrated by Schirmer testing) in up to 59% of patients after six months of treatment.5 Additionally, a reduction in conjunctival T-lymphocyte infiltration

was noted after six months of cyclosporine therapy.6

Allergan heralds Restasis as the first drug proven to effectively treat a cause of dry eye disease, rather than only temporarily alleviate symptoms. But although this product has yielded good results in clinical trials, practitioners have been somewhat reluctant to actively prescribe Restasis for several reasons. First, many are confused as to precisely which dry eye patients will benefit from this therapy. Second, ocular burning has been reported as an adverse event in up to 17% of individuals utilizing the drug.5 Third, the time frame of six months may seem irrationally long for

some practitioners and patients to observe improvement in the disease course (even though many patients experience improvement after only a few weeks). Finally, the retail cost of Restasis is somewhat expensive as compared to conventional therapy, on the order of $80 to $100 per month. While these issues cannot be ignored, the fact remains that Restasis may offer great potential benefit to many of our patients. Practitioners need to remain open minded and

personally evaluate this product on at least a few patients before reaching the conclusion that it is too slow, too uncomfortable or too expensive. Restasis is prescribed on a bid basis.

(21)

More products remain under investigation for the treatment of dry eye syndrome. Diquafosol tetrasodium, a topical agent referred to as INS365 Ophthalmic by Inspire Pharmaceuticals, has been shown to activate P2Y2 receptors in the mucosal cells of the palpebral conjunctiva.7,8 These

receptors are believed to regulate a variety of cellular responses.

When used topically on the ocular surface, INS365 has been shown to pull salt, water and mucin from conjunctival cells, effectively creating an artificial tear comprised of purely endogenous components.7 Inspire Pharmaceuticals filed a new drug application for INS365 in June 2003, and

received an approvable letter from the FDA on December 22, 2003. A launch of this product is anticipated sometime in 2004.

Still in clinical trials is 15(S)-HETE (15-hydroxyeicosatetraenoic acid) from Alcon Laboratories. Like INS365, this product is best described as a secretagogue, in that it induces secretions from bodily tissues. Specifically, when instilled in the eye, 15(S)-HETE stimulates production of the glycoprotein Muc1.9 Muc1 is an important component of the tear mucin layer; enhancement of

this element may help to alleviate corneal injury and restore corneal integrity in dry eye patients.

Choroidal Rupture

Signs and Symptoms

Patients who experience choroidal rupture are often younger and involved in activities, such as ball sports, which expose them to potential high-rate impact trauma to the eye or adenexa. Patients have a history, either recent or antecedent, of direct or contrecoup injury to the eye and surrounding structures.

Choroidal ruptures may be single or multiple and may affect any part of the posterior segment. In recent trauma, there may be hemorrhage in any layer ranging from the choroid to the vitreous. However, if the trauma was many years antecedent, there will be no hemorrhage unless choroidal neovascularization has developed. Visual acuity and visual field may be dramatically reduced or may be normal and the patient is asymptomatic.

Ophthalmoscopically, you will note a linear disruption that may be crescent-shaped. Often, the rupture will have the concave aspect toward the disc. There is usually

significant reactive RPE hyperplasia, giving the rupture a pigmented appearance.

Pathophysiology

Direct or contrecoup injury can precipitate a choroidal rupture. Hemorrhage and edema may be present initially, but will resolve. Typically, reactive hyperplasia gives the rupture a heavily pigmented appearance. Often, the overlying retina is undisturbed in choroidal rupture. However, if the RPE is disturbed and becomes hyperplastic and invades the sensory retina, visual dysfunction ensues.

Due to the subsequent disruption of Bruch’s membrane that occurs in choroidal rupture, choroidal

neovascular membranes may develop within the rupture. This may be a late development that can occur up to five years after the precipitating trauma.

Figure

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References

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