characteristics (deferred treatment) developed. Methods A Markov model with a 30-year time horizon was developed, in which patients presenting with moderate NPDR could progress through all stages of DR (severe NPDR>early PDR>HR-PDR>severe PDR) to severe vision loss and blindness (and to death). A National Health Service and personal social services perspective was adopted. Transition probabilities were mainly derived from the Early Treatment DiabeticRetinopathy Study. Health state utilities, costs and complications were based on information from the literature, supplemented by expert opinion. Costs and outcomes were discounted at 3.5%. Both deterministic and probabilistic sensitivity analyses were conducted. Results Administering PRP at the severe NPDR stage could be more effective and less costly than waiting until HR-PDR developed. Sensitivity analyses gave similar results, with early treatment continuing to dominate deferred treatment. The probabilistic sensitivity analysis suggests that at willingness-to-pay threshold of £20 – £30 000 per quality-adjusted life year, the probability of early treatment being cost-effective is 60%.
However, the evaluation has various shortcomings. First and most notably is the use of progression data mainly from the ETDRS trial. 6 More recent studies have been conducted but they have not addressed the issue of early versus delayed PRP (timing). Due to improved treatments, better blood glucose control and population screening, monitoring and intervention, there has been a reduction in the incidence of severe vision loss/blindness from DR. 2 4 Second, even though we conducted a thorough search of the literature, we did not identify any studies with health state utility values by the detailed severity levels that we have in our model or data on disutilities associated with progressing through all the different stages of DR, or data on the disutilities after PRP, especially following the use of modern laser delivery devices. We had to rely heavily on two papers 9 10 to characterise the different visual acuity levels into health states and link them to the utility values for patients with DR as reported in Brown et al . 8 The key limitation from this
and HbA1c levels have a positive correlation to the onset and progression of DR. VEGF, a mito- gen for endothelial cells, is a key angiogenic factor for stimulating new vessel formation and vascular hyper-permeability in DR, and due to its expression both in-vivo and in-vitro can be induced by retinal hypoxia . DR results in a series of changes, including increased retinal vascular permeability, chronic retinal hypoxia and extensive retinal ischemia; the processes of which are thought to be mediated by vari- ous growth factors such as VEGF . HbA1c is regarded as a biochemical model for the patho- genesis of DR through glycosylation reactions . The metabolic control, reflected by blood glucose level and HbA1c value, accounts for an important factor for the onset and progression of DR, making HbA1c varying with DR progres- sion . Early epidemiologic studies show a critical relationship between HbA1c levels and the incidence of DR, making it feasible to avoid progression of DR with tight glycemic control . Cavusoglu et al.  argue that progres- sively increasing VEGF serum and HbA1c le- vels bear a correlation with the degree of DR, which is in agreement with our results. The- refore, VEGF serum and HbA1c levels are asso- ciated with the severity of DR in patients. The same study also argues that VEGF serum and HbA1c levels are down-regulated after laserphotocoagulation in DR patients, and that VEGF serum and HbA1c levels in the NPDR group were significantly lower when compared to the PDR group. Laserphotocoagulation, in which laser burns are placed over the entire retina except the central macula, is an estab- lished technique for treating severe DR . It promotes regression and arrests progression of retinal neovascularisation while ameliorating retinal ischemia and hypoxia, thus inhibiting VEGF activity and causing a reduction in isch- emia-driven VEGF production, which eventually causes VEGF serum levels to decrease . The same result was observed by Lip et al. in their pilot study, where they suggest that the angiogenic stimuli responsible for increased VEGF appeared to decrease during laser photo- coagulation . Qiao et al. found that laser pho- tocoagulation can reduce VEGF serum and HbA1c levels , which is in agreement with our studies. In addition, it was found that the lower the VEGF and HbA1c levels were, the bet- ter the visual acuity recovery and therapeutic
Non-ophthalmic doctors can have a retinopathy detection rate of 49% compared to 96% for ophthalmologists . Therefore, a costeffective method for screening is essential for diabeticretinopathy. Screening by digital photography proposed under the National Service Framework is offered to all patients with diabetes in the United King- dom. It is supplemented by biomicroscopy by the oph- thalmologists in monitoring and treating sight threatening disease. Furthermore, optical coherence tom- ography has become a powerful tool in screening and monitoring CSMO with sensitivity and specificity rates of near 80% and 90%, respectively . Perhaps with fur- ther investigation, TCCT testing may become a supple- ment for detecting and monitoring sight threatening pathology without much equipment or trained techni- cians. However, with current data, all forms of TCCT test- ing including the Chromatest do not qualify for use in screening for CSMO.
As expected, the highest clinical outcomes are obtained with the age 30 scenario (0.804 QALYs gained, 0.466 DALYs averted and 7.068 years of severe visual impairment avoided per patients) due to longer time spent in the model by the cohort. The other four scenarios are associated with the same outcomes as only costs were varied: 0.523 QALYs gained, 0.273 DALYs averted and 2.199 years of severe visual impairment avoided per patient. The per- patient costs of the intervention are: $195 for the -20% of salaries scenario, $209 for the base case, $224 for the +20% of salaries scenario, $256 for the age 30 scenario, and $274 for the 50% utilization rate scenario. From a health provider perspective and compared with no screening and no treatment, the intervention in the base case has an ICER of $400 per QALY gained. The lowest ICER is obtained with the age 30 scenario ($318 per QALY) while the 50% utiliza- tion rate scenario is the least cost-effective ($523 per QALY). The impact on the ICER of an increase ($428 per QALY) or a reduction ($372 per QALY) by 20% in the staff salaries is rela- tively small. Using the WHO threshold for low-income countries [20,29], in the base case and all the sensitivity scenarios explored the intervention appears cost-effective (<3x GDP/capita) but not highly cost-effective (<1x GDP/capita).
Patients were included if they had: type 1 or 2 diabetes, been recommended for panretinal photocoagulation; vision acuity of 20/100 or better; spherical equivalent of ± 6.00 spherical diopters. Exclusion criteria related to the eye were: previous retinal photocoagulation or cryopexy of any kind; dense cataract or vitreous opacity; retinal disease other than diabeticretinopathy; ocular hypertension or glaucoma (IOP higher than 21 mmHg and/or cup disk ratio equal to or higher than 0.8) or other optic nerve diseases; and ocular surgery within the last 6 months, including laser treatment. Systemic exclu- sion criteria were: known immunological condition/disease; active infection within 30 days prior to enrolment (eg, urinary tract infection, upper/lower respiratory tract infection, skin infection, arthritis); use of interferon or immunosuppres- sive, cytotoxic or corticosteroid chemotherapy or lymphoid irradiation within 1 year prior to study entry; serious disease
PRP was performed by single trained personnel. An argon green 532 nm (Ellex SOLITAIRE, FL, USA) laser machine was used. A total of 900 to 1200 laser spots were required for each setting. Spot size was 200 µm and pulse duration 100 milliseconds. Power was adjusted to attain grey burns and spots were placed one spot distance apart. Repeated PRP lasering was performed in two to four sessions until the new vessels regressed. Fundus was reviewed by another qualified observer to determine the sufficiency of treatment. Intervals between the laser sessions were fixed at 1 to 2 weeks. The total laser spots over the entire treatment period ranged from 2,000 to 2,500 shots. Repeat OCT was performed 2 and 4 months after treatment.
Main outcome measures The primary outcome was the proportion of patients with an improvement in best corrected visual acuity of more than two lines on the Early Treatment DiabeticRetinopathy Study (ETDRS) scale. Secondary outcomes included mean changes in best corrected visual acuity and in central macular thickness, and adverse events. Best corrected visual acuity was converted to logMAR units, a linear scale of visual acuity with positive values representing increasing visual loss. Indirect comparisons were done using Bayesian methods to estimate relative treatment effects of bevacizumab and ranibizumab. Results Five randomised controlled trials with follow-up of 6–12 months and a common comparator (multiple laser treatment) were sufficiently similar to be included in the indirect comparison. Generally studies were small, resulting in wide credible intervals. The proportions of patients with an improvement in best corrected visual acuity of >2 lines were 21/77 participants (27%) for bevacizumab and 60/152 participants (39%) for ranibizumab (odds ratio 0.95 (95% credible interval 0.23 to 4.32)). The wide credible intervals cannot exclude a greater improvement, or worse outcome, for either drug. The mean change in best corrected
and DME as there are many options that have not been rigorously tested through large, randomized, controlled clinical trials. Conclusion: Pharmacotherapy, both ocular and systemic, will be the primary mode of interven- tion in the management of DR and DME in many cases when cost and treatment burden are less constrained. Conventional laser therapy has become a secondary intervention in these instances, but remains a ﬁ rst-line option when cost and treatment burden are more constrained. Results with subthreshold laser appear promising but will require more rigorous study to establish its role as adjunctive therapy. Evidence to support an optimal integration of the various treatment options is lacking. Central to the widespread adoption of any therapeutic regimen for DR and DME is substantiation of safety, ef ﬁ cacy, and cost-effectiveness by a body of sound clinical trials. Keywords: diabetes, retina, diabeticretinopathy, diabetic macular edema, neovascularization, laserphotocoagulation, intravitreal injection, vascular endothelial growth factor, vitrectomy pars plana vitreous surgery, antiangiogenic therapy
Regarding the severity of DR, 57.8% of affected patients had non-proliferative DR on angiography, a finding in agreement with the 68.7% found by Nanfack et al. in Yaoundé, Cameroon . The diabetic maculopathy rate was 14.5% in our study. This is about twofold the preva- lence found by Nanfack et al. (7.15%) in Cameroon, Rema et al. (6.4%) in India and Khandekar et al. (6.3%) in Oman [21-23]. Seventeen point four percent of our patients had at least severe non-proliferative DR and thus required treatment by laserphotocoagulation. Of these patients, 66.2% had a treatment. This is a good treatment uptake coverage compared to the 26.7% reported by Nanfack et al. in Yaoundé, Cameroon . However, these findings emphasize the need of increasing the access to treatment for the patients affected by DR. In this way, the treatment outcomes in our study are encouraging: 73% of the pa- tients who were treated and who had an angiography two months after treatment for control had an improvement. The association of severe proliferative DR with a poor treatment outcome in our study highlights the necessity of early diagnosis and treatment. The numerous cases of severe retinal disease found in our study is a call for the introduction vitreoretinal surgery in the routine ophthal- mologic practice in Cameroon.
Abstract: In this study, changes in Retinal Nerve Fiber Layer (RNFL) within peripapillar zone in patients with diabeticretinopathy that accomplish criteria to receive panretinal photocoagulation are analyzed by TD-OCT (Time Domain-Optic Coherence Tomography) unit. This analysis was transversal retrospective and observational and was done in 46 eyes from 33 patients. According to laser application technique, time since application and day of the study, 4 groups of patients were set: the first with patients with less than 30 days since last laser application and day of study. The second with patients with 180 days since laserphotocoagulation; the last two groups received panretinal photocoagulation plus macular selective laser with a TD-OCT performed 30 days (for the third group) and 180 days (the fourth group) after administration of treatment. The clinically significant finding was in comparing the group that received panretinal photocoagulation with TD-OCT after 30 days, and the group that received panretinal photocoagulation and TD-OCT after 180 days. Average thickness was less in the second group, with a statistical significant finding p=0.012 in inferior quadrant. Administer laserphotocoagulation makes changes in the structure and function of the retina, and according to references many different results may be possible taking in count the equipment used to apply treatment and to take measurements. The patient must be informed about secondary and adverse effects after the treatment
Despite of the advent of anti-VEGFs in treatment of DR, laserphotocoagulation still plays a vital role in management of DR and will continue to be a pivotal component for the next several years. 19 In the multicentre randomized clinical trial by the DRCR network it had been shown that over a two year period, focal/grid photocoagulation was more effective and had fewer side effects than 1-mg or 4-mg doses of preservative-free intravitreal triamcinolone for most patients with DME. The study supported the fact of focal/grid laserphotocoagulation being effective in the treatment of DME. 20 The results of the RESTORE study by Mitchell et al. 21 advocate a combined modality of treatment for DME in the form of ranibizumab with laserphotocoagulation. Excellent to good eyesight was reported by 50% of the patients who had taken a combined treatment (determined by the individual NEI VFQ-25 question pertaining to patient’s perception of eyesight post-treatment). The present study shows that laserphotocoagulation has a distinct role in maintaining a stable visual acuity in patients with DR. Improvement in CS is the maximum after focal laser in CSME due to the subsidence of macular edema. Majority of the patients demonstrate no change in the self reported visual disability after laser treatment (60.4%) while only a few patients experienced a worsening (3.8%).
Since VEGF contributes to the development of macular edema, attention has recently focused on intravitreal injections of anti-VEGF antibodies. Antibodies delivered by intravitreal injection bind to VEGF and thereby decrease downstream effects on vascular leakage. Anti-VEGF antibodies were ﬁ rst used to treat patients with exudative age- related macular degeneration (AMD) with dramatic beneﬁ cial results. Because of these beneﬁ ts, anti-VEGF antibodies are now being evaluated in the treatment of macular edema.
particular, the modified classification used in the ETDRS has been used widely in research settings but involved a complex scoring system ranging from 10 to 85 and required comparison with the standard photographs. 12 As a result, even more simplified, clinical classification systems are more commonly used nowadays. 13,14 However, whether more granular, feature-based criteria can predict PDR progression in a large scale has not been studied to our knowledge. In addition, progression rates of retinopathy in the context of current systemic management have not been adequately explored with real world data. This information will be important in guiding follow-up intervals on monitoring for diabeticretinopathy, advising the patient and their diabetic care team regarding progression risk, as well as the powering of clinical trials for interventions that may prevent the progression of diabeticretinopathy.
This study was carried out in Oulu University Hospital. The retrospective interventional case series was performed on all adult patients who presented at Oulu University Hospital with either type 1 (T1D) or type 2 diabetes (T2D) complicated by VH due to PDR between 1 January 2011 and 31 December 2015. The hospital’s elec- tronic patient database was used to search the potential study patients by using the International Classification of Diseases diagnose codes for diabetes, PDR and VH. When the fundus of a patient could not be visualised due to VH, an ultrasonography examination was performed in order to exclude any tractional or other retinal detachment that would have been contraindicative for intravitreal anti- VEGF treatment. Only patients with naive eyes for PPV were included for the study and those with a history of prior PPV before beginning of the follow- up period were excluded from the statistical analysis (n=4). Exclu- sion was also made if the follow- up period was less than a 1 year (n=3). Subjects who had VH for reasons other than PDR (eg, retinal vein occlusion, retinal detachment or retinal breaks) were also excluded. After identifying the potential study subjects, a chart review of the patients’ demographic information was made, consisting of treat- ments used for VH (IVB, PRP, PPV) and spontaneous resorption, best corrected visual acuity (BCVA), intra- ocular pressure, iris NV and lens status. Patient records were also reviewed for dates of IVB, PRP, PPV, sponta- neous resorption and the status of each VH during the study period. BCVA measurements were converted to a logarithm of the minimum angle of resolution (logMAR) for analysis.
At present, in Vietnam, advances in neonatology allow survival of children with extremely low gestational age and weight at birth, leading to an increase in the number of patients with ROP. Refractive error is a known complication of ROP and its treatment, and is a common cause of vision impairment in children. It is also treatable. Therefore, we initiated this study to evaluate the refraction of eyes treated with diode laserphotocoagulation for prethreshold ROP at a mean of 5 years after treatment.
Crystallin was initially reported as a constituent protein of the lens, with later reports indicating its expression not only in the lens but also in the ciliary body, the neural retina, and retinal pigment epithe- lium [1, 2]. It has previously been reported that the retinas of diabetes patients have higher-than-normal expressions of αA-crystallin, and that its production is induced by glycated proteins, i.e., the accumulation of advanced glycation end-products (AGE) in the eye . Here, we report a case of proliferative diabeticretinopathy (PDR) in which a scintillating substance that appeared to be crystallin developed in the intra- vitreal cavity after laserphotocoagulation.
within one disc diameter of the center of the macula. The lesion is considered usually associated with adjacent retinal thickening and is predictive of the presence of macular edema [7,8]. On retrospectively analyzing the seven standard fields form and the ETDRS photographic data base, such criteria have a sensitivity of 94% for detection of clinically significant macular edema . In case the existence of hard exudates in the central macu- lar field is suspected, but cannot be confirmed, a visual acuity below 63 ETDRS letters (20/62.5) will trigger an automatic diagnosis of macular edema. Medical advice to the diabetic participants included mainly two recom- mendations: (1) consulting an experienced ophthalmolo- gist for further in-person eye examination after pupil dilation, as soon as possible, in cases of moderate non- proliferative DR (NPDR), or worse , macular edema or ungradable photographs; or (2) attending another eye screening within the next year in case of normal appear- ance or mild NPDR. The criteria for ungradable images were the same in former reports: when the large vessels of the temporal arcades were blurred or more than one- third of the picture was blurred unless referable retino- pathy was detected, an eye was considered ungradable . When unexpected diseases were detected that required urgent attention, the reader promptly phoned the PCPs. The engineer in the data server downloaded the reader-generated reports, saved them into the data- base, and provided print-copies to the PCPs, who later informed the participants and scheduled the next screening time if accepted.
In 2004, the American Telemedicine Association estab- lished consensus recommendations that provided guidelines for clini- cal, technical, and operational performance standards for diabeticretinopathy screening. The develop- ment of retinal imaging and, more recently, digital retinal photography may help address the barriers to access for retinopathy screening. Telehealth (telecommunication to promote health) or telemedicine (telecommunication for diagnos- tic and therapeutic intervention) programs based on retinal imaging with or without remote interpreta- tion may facilitate early diagnosis of diabeticretinopathy and timely treatment, hence preserving vision. 28
The use of an ellipsoidal mirror means that the 200 ° images produced by the Optomap UWFSLO are not uni- formly focused but instead have a sharper focus in the center and are progressively more distorted toward the periphery. However, there is a substantial amount of peripheral retina outside the ETDRS seven-field view sharp enough to allow DR grading (Figure 1). Silva et al 14 compared the grading