Optic Nerve Head

The pathogenesis of ONH alteration in these patients was probably related to a reduction in ocular perfusion second- ary to heart failure. However, we cannot rule out a possible thromboembolic etiology for the changes of the optic nerve found in patients with CHF because cardiovascular disease is an important risk factor for thrombotic events. However, this Table 5 Correlation between the cardiovascular parameters and stereometric measurements of the optic nerve head in patients with chronic heart failure

Increased levels of ET-1 have been known to lead to a reduction in blood flow in both the choroid and the optic nerve head [19]. ET-1 constricts vessels both dir- ectly and indirectly by increasing the sensitivity to other vasoconstrictive hormones such as norepinephrine, 5- hydroxytryptamine, and angiotensin-II. An increase in circulating ET-1 markedly reduces blood flow in the eye [20]. If the concentration of ET-1 is even higher, it causes vasospasm [21]. The stimulation of ET receptors on smooth muscle cells or pericytes increases cytoplas- mic calcium, both by influx into the cell, as well as by liberation of calcium from the internal storage [22]. High levels of ET-1 in the eye cause pro-inflammatory cyto- kine overproduction and oxidative stress pathway activa- tion, as well as reduced trophic support and oxygen delivery to the retina [23].

Each subject underwent a full ophthalmic examin- ation, which included measures of visual acuity, refrac- tion, intraocular pressure (IOP) by a noncontact tonometer. Axial length measurements were obtained in each eye with the IOL Master (Carl Zeiss Meditec, Inc, Dublin, CA), CA measurements were obtained by a Topolyzer (Allegretto Wave Topolyzer, Germany), optic nerve head evaluation was performed with a 90-D lens, and peripapillary RNFL thickness and ONH parameters were measured with the Cirrus HD OCT (Cirrus HD OCT; Carl Zeiss Meditec, Dublin, CA). The peak loca- tions of the superotemporal and inferotemporal areas were evaluated by the RNFL TSNIT curve of the Cirrus HD OCT. The peak locations, which were measured by the RNFL TSNIT curve, were translated to units of degrees by multiplying 360/256. For example, the super- ior peak location of 40 in the TSNIT curve was trans- lated to 56.25 degrees (40 × 360/256 degrees). This means that the thickest superior RNFL was located at the point 56.25 degrees away from the temporal hori- zontal meridian. We defined α angle as the angle be- tween the horizontal meridian and superotemporal peak location by clockwise rotation, and the angle between the horizontal meridian and inferotemporal peak loca- tions by counterclockwise rotation were defined as β angle (Figure 1).

was compared with the predicted rim area adjusted for disc size and age. The normative database was compared in six regions (superior temporal, inferior temporal, temporal, superior nasal, inferior nasal, and nasal) and as an overall global classification. The eyes were classified into three categories: within normal limits (WNL) 95% confidence intervals (CI); borderline (BL), 95%–99.9% CI; and outside normal limits (ONL), 99.9% CI. In the GPS calculation, parameters describing the shape of the optic nerve head and retinal nerve fiber layer were calculated based on the mathematical model derived from normal and glaucoma- tous eyes in HRT. The parameters thus obtained were used to compute the GPS numeric scores. Then, the final GPS was used for the classification was WNL (0%–27%), BL (28%–64%), and ONL (65%–100%). The AUC curves were plotted between the normal and SSOH eyes for the FSM discriminant function, MRA, and GPS. The categoric vari- able was computed where “normal” = 0, “borderline” = 1, and “outside normal limits” = 2.

Glaucoma diagnosis primarily relies on Tonometry, Perimetry and Optic nerve head (ONH) evaluation. Tonometry involves measurement of IOP. IOP is one of the factors required for primary investigation. Perimetry relies on detection of the functional change that is loss of vision. This test measures side (peripheral) vision. Peripheral vision loss is the result of Glaucoma. ONH evaluation is used for detection of structural changes in ONH. IOP alone is not indicative of Glaucoma unless it is grossly abnormal. Visual Field loss is the late manifestation of the disease. In Glaucoma, structural changes in the ONH precede functional changes in the visual field. Comprehensive examination of the patient’s ONH helps in early Glaucoma diagnosis [4, 7]. Optic disc and Retinal nerve fiber layer (RNFL) assessment can be performed according to five rules that include the evaluation of optic disc size, rim shape and area, presence of RNFL loss, presence of parapapillary atrophy and presence of retinal or optic disc haemorrhages. By following these five rules, a thorough and systematic review of the optic disc and RNFL occurs. This improves the ability to diagnose and manage glaucoma [7]. Early treatment reduces rate of progression of the disease thus preventing visual field loss and blindness. Normal eyes show a characteristic configuration of rim thickness. This is called as ISNT rule. The neuroretinal rim is broadest in the inferior rim, followed by superior and nasal rims and is thinnest in the temporal region. The ISNT rule is useful in differentiating normal and glaucomatous optic nerves [8].

Glaucoma, is the major cause for blindness [1], is initiated due to increase in intraocular pressure (greater than 21mm of Hg) and it leads to damage to optic nerve [2]. The cup to disc ratio value of more than 0.3 indicates the presence of glaucoma. The colour fundus images are used to track the same by its anatomical structures such as blood vessels, optic cup, optic disc and macula for a normal retina. In a normal eye physical diameter of the optic disc is about 1.5 mm that is placed 3 to 4 mm to the nasal side of the fovea. A small depression seen at front of the optic nerve head is known as the cup and is smaller than the optic disc. A number of studies have reported on the same. In 2006, Yandong Tang et al presented an automatic

A 20-year-old male patient presented at our clinic complaining of strange visual experiences (neither decreased nor blurred) and a mild headache while reading. His best corrected visual acuity revealed 20/20 with a fort myo- pic correction. Intraocular pressures measured with Dynamic Contour Tonometer (DCT) (Swiss Microtechnol- ogy AG, Port, Switzerland) were 23.3 mmHg in the right eye (OD) and 27.4 mmHg in the left eye (OS) with cen- tral corneal thicknesses (CCTs) of 588 (OD) and 591 (OS) microns, respectively. Optic discs were bilateral pale with indistinct and scalloped margins without cupping. Red free photos showed autofluorescence of both optic discs, representative of optic disc drusen. Visual field analysis (VFA) of both eyes revealed sensitivity depression with localized defects consistent with the Optical Coherence Tomography (OCT) findings. Optic nerve head drusen (ONHD), myopia and high intraocular pressures (IOPs), may cause ganglion cell damage resulting in RNFL thinning and visual field loss. Because of the difficulty in detecting the exact cause and the extent of the damage, patients with ONHD associated with high IOPs and myopia should be examined closely with serial monitoring using OCT and VFA. In case of RNFL thinning and visual field defects, topical antiglaucomatous therapy should also be determined.

Following blinding of clinical and demographic data, the ON and ONH in each patient (IIH and controls) were independently eval- uated by both readers. MR imaging findings were considered pos- itive if given any nonzero score on the scale in our study. Each reader found that there was a greater incidence of hyperintensity of the ON/ONH on CE 3D-FLAIR imaging among the patients with IIH than among the control group. For reader 1, hyperinten- sity of at least 1 ON was 84.4% sensitive (95% CI, 75.7%–90.4%) and 100% specific (95% CI, 96.3%–100%) for the presence of papilledema. The correlation between reader 1’s evaluation of the papilledema grade as measured on the scale of our study and the papilledema grade per the neuro-ophthalmologic Frise´n Scale was as follows: right eye (OD): ␶ ⫽ 0.48; 95% CI, 0.32– 0.61; left eye (OS): ␶ ⫽ 0.43; 95% CI, 0.24 – 0.57. For reader 2, hyperinten- sity of at least 1 ON was 77.1% sensitive (95% CI, 67.7%– 84.4%) and 87.7% specific (95% CI, 80.6%–92.5%) for the presence of papilledema. The correlation between reader 2’s evaluation of the FIG 1. CE 3D-FLAIR images obtained in 4 different patients illustrate the grades of edema seen within the optic nerve and optic nerve head on MR imaging: 0 ⫽ normal (A), 1 ⫽ mild hyperintensity of the ON without involvement of the ONH (arrows, B), 2 ⫽ moderate hyperintensity of the ONH as well as mild inversion of the ONH (arrows, C), and 3 ⫽ marked hyperintensity of the ONH with severe inversion of the ONH (arrows, D).

2. Wollstein G, Binnun E, Ben-Yosef N, Rozenman Y. Retinal thickness ana- lyzer (RTA) imaging of a model eye and the optic nerve head. Comparison with Heidelberg Retina Tomograph measurements. In: Lemij H, Schulman JS, editors. The Shape of Glaucoma, Quantitative Neural Imaging Techniques. The Haag: Kugler Publications; 2000:193–212. 3. Varma R, Steinmann WC, Scott IU. Expert agreement in evaluating

Photographs were obtained annually for all of the patients using a simultaneous stereoscopic camera (3-Dx; Nidek Co., Ltd., Gamagori, Japan) after maximum pupil dilation. For each eye, the photographs obtained at baseline and at the most recent follow-up visit were randomly assigned to be labelled as A or B, to mask the temporal order. All other information about the eye and the patient was masked from the graders, including the appearance of the fellow eye. Two fellowship- trained glaucoma specialists independently viewed the baseline and final follow-up photographs sequentially using a Stereo Viewer II (Asahi-Pentax, Tokyo, Japan) and graded them as “changing” or “stable”, indicating which photograph showed worse damage (A or B). If there was change, the type of change was recorded, as one or more of the following: increased neuroretinal rim narrowing, increased excavation, new or increased retinal nerve fibre layer defect or new notching. The location of change was recorded in 90 degree sectors (0 ˚ -90˚, 90˚-180˚, 180˚-270˚ and 270˚-360˚). Quality assessments of each image pair were recorded separately for clarity and for stereopsis as ‘excellent, ‘adequate’ or ‘unacceptable’.

strong activation of a subset of AP-1 regulated targets shown in Table 5. Co-activation of transcription factors AP-1 and NF-  B in glaucomatous ONHAs is consistent with their parallel regulation via TLR receptors and MyD88 [59-62], and a synergistic role in promoting cell response and survival to various stresses [63]. Impor- tantly, the gene encoding GATA-3, a transcriptional regu- lator of TLR2, was elevated in glaucomatous ONHAs. The activation of AP-1/c-Fos/c-Jun complex has been well characterized recently in primate model of glaucoma [5]. We compared relative connectivity (experimental vs. expected) of the top five transcription factors and within the list of activated genes (2.5 fold) using the MetaCore Interactome characterization tool ([64] see also descrip- tion in -Methods). Although NF-kB forms only the third largest module (32 edges, 27 activated targets) in the net- work, interactome analysis showed it as the most over- connected one within activated data set (see Additional File 1, Supplement Table S5). Combined with a well- defined role in regulation of inflammation [2,63-66], responses to stressors (cytokines, complement factors [67] and reactive oxygen species [64,68,69]), this result may suggest that NF-kB is the key regulator of neurotoxicity in reactive ONHAs in human glaucoma. Four NF-  B subu- nits, c-REL, RELA, NFKB2 and NFKBIA, showed activation at transcriptional level (see Additional File 2). Our data showed elevated expression of several upstream regulators of NF-  B (AR, EGR3, GATA3 and SATA3/BST2), as well as downstream targets in glaucomatous ONHAs (Figure 4A). Transcriptional changes in other well known activators of NF-  B and AP-1, such as TNF  , IL-1  , and TLRs were below the cut-off level of our analysis, and examination of post-translational activation of those was outside the scope of this study. Alternatively, we performed immuno- histochemical analysis of optic nerve slices from human donor tissue (see Additional File

For each eye, total, superior, and inferior peripapillary retinal nerve fiber layer (pRNFL) thicknesses were evaluated by ONH and automatically calculated by OCT using existing software. The 3D OCT 2000 (software Version 8.00; Topcon Corporation) automatically detects the disk center by refer- ring to the infrared reflectance image. Based on the inputted refractive information, the software adjusts the circle diameter for the circle scan and corrects papillary diameter, area, and volume, while also calculating magnification compensation, which enables accurate scanning. The machine automatically detects the edge of the optic disk as the end of the retinal pigment epithelium/choriocapillaris.

Patients and methods: This prospective study compared 58 patients with early glaucoma and PCS to 58 age-matched control individuals. All glaucomatous eyes had scotoma within the central 12 degrees of fixation and confined to one hemifield. We measured circumpapillary retinal nerve fiber layer (cpRNFL) thickness, macular ganglion cell-inner plexiform layer (GCIPL) thickness, and optic nerve head (ONH) parameters with Cirrus spectral domain optical coherence tomography. Macular ganglion cell asymmetry was expressed as the absolute differences and the ratios between the inferior and superior hemispheres, inferotemporal (IT) and superotemporal (ST) areas, IT and superonasal (SN) areas, IT and inferonasal (IN) areas, and ST and IN areas. The asymmetry index was the absolute log 10 of the ratio. The area under the receiver operat- ing characteristics curve (AUROC) and partial AUROC (pAUROC, specificities $90%) were analyzed for each parameter.

The Blue Mountain Study has shown that cup- disc ratio is strongly associated with disc diameter and optic discs with larger vertical diameters have considerably greater vertical cup- disc ratios [5]. Measured values of optic disc size vary with the measurement technique utilized [6]. Disc size is known to vary largely between race, sex and between eyes with Africans noted to have large disc sizes as compared to other race [3,7]. It is often easier to detect a glaucomatous appearing optic nerve head if the disk is large compared to one that is small. The disc size itself may influence the likelihood that a clinician makes a diagnosis of glaucoma, thus providing a potential source of bias [6].

AION could be arteritic; (caused by severe vasculitis) as in giant cell arteritis or non-arteritic. Nonarteritic anterior ischemic optic neuropathy is the result of the interruption of oxygen supply to the optic nerve head anterior to the lamina cribrosa, and the major contributing factors include failure of perfusion pressure resulting from a severe drop in blood (such as in systemic hemorrhage and surgical hypotension), critical decline of oxygen-transport by the blood (such as in severe anemia due to blood loss), and increased resistance to blood flow such as in atherosclerosis, polycythemia, and small optic disc (Kenkel et al., 2004). Posterior ischemic optic neuropathy, on the other hand, usually occurs in the setting of severe anemia and hypotension caused by hemorrhage from surgery and gastrointestinal bleeding, even in healthy subjects with no systemic vascular risk factors (Murphy, 2003).

The diagnosis of ONH remains primarily clinical, with no universal guidelines for laboratory or radiographic tests to establish a diagnosis. Because of this, optic nerve hypo- plasia patients may mistakenly be labeled with alternative disease states, including optic atrophy. 2 Although severe cases of ONH are often easily diagnosed, subtle presenta- tions can be dif fi cult to diagnose clinically. Current diag- nostic standards for ONH include comparing a disc to macula (DM) and disc diameter (DD) ratio against that of the general population. Yet this DM:DD ratio varies with age, race, and gender. 6 Most clinicians believe that neither this DM:DD ratio, nor other clinical signs (e.g., double-ring sign, vascular signs) are pathognomonic for ONH. 2 Thus, diagnosing and rating severity of ONH is dif fi cult. The application of Optical Coherence Tomography (OCT) Spectralis to evaluate for the retinal nerve fi ber layer (RNFL) thickness at the optic nerve head and to determine severity of ONH may improve consis- tency of diagnosis.

the last few years, many imaging systems have been proposed and supported for the quantitative assessment of morpho- logical changes in glaucoma, which relate to the optic nerve head (ONH) and the optic fiber layer, with optical coherence tomography (OCT) and Heidelberg retina tomograph (HRT) the most known. The OCT is an optical analog of b-ultrasound based on light emission wavelength near the infrared spectrum (840 nm) and generates optical tissue sections with resolution of the order of 10–15 µ m (OCT 2) and 10.8 µ m (OCT 3). It is able to measure the thickness of the peripapillary nerve fiber layer, a method that has been proven by studies to have good sensitivity and specificity in the discrimination of glaucoma and non-glaucoma patients. 8–12 The Heidelberg retina tomograph

The patient was admitted to the rheumatology service of our hospital for suspect silent GCA, and high dose corticosteroid therapy was immediately started (1 g methilprednisolone/day i.v. in the first three days, then oral prednisone 50 mg/day). The patient did not report any change of the visual symptoms after starting the corticosteroid therapy. A brain MRI was performed three days after presentation, showing bilateral optic nerve head thickening and multiple chronic ischemic lacunae in sub- cortical and profound white matter. The ultrasound study of the temporal arteries showed tortuosity and segmental stenosis of the arterial lumen, without sig- nificant limitation of the blood flow. Ultrasound mor- phologic alterations typical of GCA (hypo-ecogenic concentric mural thickening) were not found. Carotid Doppler-ultrasound did not identify significant alter- ations of blood flow.

22. Rao HL, Kumar AU, Babu JG, Kumar A, Senthil S, Garudadri CS. Predictors of normal optic nerve head, retinal nerve fiber layer, and macular parameters measured by spectral domain optical coherence tomography. Investigative Ophthalmology and Visual Science. 2011;52(2):1103-10. 23. Sull AC, Vuong LN, Price LL, Srinivasan

Glaucoma is an eye disease that leads to poor vision and eventually blindness. Detecting the disease in time is important as it cannot be cured. It is a second leading cause of blindness. It is predicted that around 80 million people will be affected by 2020. It cannot be cured but by using different techniques and medical treatments the progression of the disease can be slowed down. Many people are unaware of the disease until it reaches at advance level. Vision loss from glaucoma is irreversible. This motivates one to find techniques which recognize glaucoma before it reaches to blindness. Optic nerve head segmentation is one of the methods to detect glaucoma. Nerve head comprise of optic disc and optic cup. They can be detected using segmentation. Then cup to disc ratio is taken. If this ratio exceeds threshold then it is glaucomatous otherwise healthy. In this way, glaucoma can be detected so that treatment can be done to slow down the development of the disease.