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Importance: A deep learning system (DLS) is a machine learning technology with potential for screening diabetic retinopathy and related eye diseases.Objective: To evaluate the performance of a DLS in detecting referable diabetic retinopathy, vision-threatening diabetic retinopathy, possible glaucoma, and age-related macular degeneration (AMD) in community and clinic-based multiethnic populations with diabetes.Design, Setting, and Participants: Diagnostic performance of a DLS for diabetic retinopathy and related eye diseases was evaluated using 494 661 retinal images. A DLS was trained for detecting diabetic retinopathy (using 76 370 images), possible glaucoma (125 189 images), and AMD (72 610 images), and performance of DLS was evaluated for detecting diabetic retinopathy (using 112 648 images), possible glaucoma (71 896 images), and AMD (35 948 images). Training of the DLS was completed in May 2016, and validation of the DLS was completed in May 2017 for detection of referable diabetic retinopathy (moderate nonproliferative diabetic retinopathy or worse) and vision-threatening diabetic retinopathy (severe nonproliferative diabetic retinopathy or worse) using a primary validation data set in the Singapore National Diabetic Retinopathy Screening Program and 10 multiethnic cohorts with diabetes.Exposures: Use of a deep learning system.Main Outcomes and Measures: Area under the receiver operating characteristic curve (AUC) and sensitivity and specificity of the DLS with professional graders (retinal specialists, general ophthalmologists, trained graders, or optometrists) as the reference standard.Results: In the primary validation dataset (n = 14 880 patients; 71 896 images; mean [SD] age, 60.2 [2.2] years; 54.6% men), the prevalence of referable diabetic retinopathy was 3.0%; vision-threatening diabetic retinopathy, 0.6%; possible glaucoma, 0.1%; and AMD, 2.5%. The AUC of the DLS for referable diabetic retinopathy was 0.936 (95% CI, 0.925-0.943), sensitivity was 90.5% (95% CI, 87.3%-93.0%), and specificity was 91.6% (95% CI, 91.0%-92.2%). For vision-threatening diabetic retinopathy, AUC was 0.958 (95% CI, 0.956-0.961), sensitivity was 100% (95% CI, 94.1%-100.0%), and specificity was 91.1% (95% CI, 90.7%-91.4%). For possible glaucoma, AUC was 0.942 (95% CI, 0.929-0.954), sensitivity was 96.4% (95% CI, 81.7%-99.9%), and specificity was 87.2% (95% CI, 86.8%-87.5%). For AMD, AUC was 0.931 (95% CI, 0.928-0.935), sensitivity was 93.2% (95% CI, 91.1%-99.8%), and specificity was 88.7% (95% CI, 88.3%-89.0%). For referable diabetic retinopathy in the 10 additional datasets, AUC range was 0.889 to 0.983 (n = 40 752 images).Conclusions and Relevance: In this evaluation of retinal images from multiethnic cohorts of patients with diabetes, the DLS had high sensitivity and specificity for identifying diabetic retinopathy and related eye diseases. Further research is necessary to evaluate the applicability of the DLS in health care settings and the utility of the DLS to improve vision outcomes. [ABSTRACT FROM AUTHOR]

Importance: Panretinal photocoagulation (PRP) is the standard treatment for reducing severe visual loss from proliferative diabetic retinopathy. However, PRP can damage the retina, resulting in peripheral vision loss or worsening diabetic macular edema (DME).Objective: To evaluate the noninferiority of intravitreous ranibizumab compared with PRP for visual acuity outcomes in patients with proliferative diabetic retinopathy.Design, Setting, and Participants: Randomized clinical trial conducted at 55 US sites among 305 adults with proliferative diabetic retinopathy enrolled between February and December 2012 (mean age, 52 years; 44% female; 52% white). Both eyes were enrolled for 89 participants (1 eye to each study group), with a total of 394 study eyes. The final 2-year visit was completed in January 2015.Interventions: Individual eyes were randomly assigned to receive PRP treatment, completed in 1 to 3 visits (n = 203 eyes), or ranibizumab, 0.5 mg, by intravitreous injection at baseline and as frequently as every 4 weeks based on a structured re-treatment protocol (n = 191 eyes). Eyes in both treatment groups could receive ranibizumab for DME.Main Outcomes and Measures: The primary outcome was mean visual acuity change at 2 years (5-letter noninferiority margin; intention-to-treat analysis). Secondary outcomes included visual acuity area under the curve, peripheral visual field loss, vitrectomy, DME development, and retinal neovascularization.Results: Mean visual acuity letter improvement at 2 years was +2.8 in the ranibizumab group vs +0.2 in the PRP group (difference, +2.2; 95% CI, -0.5 to +5.0; P < .001 for noninferiority). The mean treatment group difference in visual acuity area under the curve over 2 years was +4.2 (95% CI, +3.0 to +5.4; P < .001). Mean peripheral visual field sensitivity loss was worse (-23 dB vs -422 dB; difference, 372 dB; 95% CI, 213-531 dB; P < .001), vitrectomy was more frequent (15% vs 4%; difference, 9%; 95% CI, 4%-15%; P < .001), and DME development was more frequent (28% vs 9%; difference, 19%; 95% CI, 10%-28%; P < .001) in the PRP group vs the ranibizumab group, respectively. Eyes without active or regressed neovascularization at 2 years were not significantly different (35% in the ranibizumab group vs 30% in the PRP group; difference, 3%; 95% CI, -7% to 12%; P = .58). One eye in the ranibizumab group developed endophthalmitis. No significant differences between groups in rates of major cardiovascular events were identified.Conclusions and Relevance: Among eyes with proliferative diabetic retinopathy, treatment with ranibizumab resulted in visual acuity that was noninferior to (not worse than) PRP treatment at 2 years. Although longer-term follow-up is needed, ranibizumab may be a reasonable treatment alternative, at least through 2 years, for patients with proliferative diabetic retinopathy.Trial Registration: clinicaltrials.gov Identifier: NCT01489189. [ABSTRACT FROM AUTHOR]

Objective: To determine the impact of ranibizumab 0.5 mg on patient-reported visual function over 36 months in individuals with visual impairment from diabetic macular edema.Methods: RESTORE comprises a phase 3, randomized, multicenter, 12 month core study and a 24 month open-label extension study. Eyes assigned to ranibizumab in the core study received ranibizumab for 36 months; eyes assigned to laser monotherapy in the core study received ranibizumab during the extension. The primary outcome was least-squares mean change in National Eye Institute 25-item Visual Functioning Questionnaire (NEI VFQ-25) overall composite and subscale scores.Results: Of 303 core study participants, 240 (79%) entered the extension, comprising 83 (35%) participants initially assigned to ranibizumab, 83 (35%) assigned to ranibizumab plus laser combination therapy, and 74 (31%) assigned to laser monotherapy. Least-squares mean (standard error) change in NEI VFQ-25 composite score from baseline to month 12 (+5.9 [1.5]; +5.0 [1.5], for the ranibizumab and combination therapy groups, respectively) decreased by month 36 (+4.1 [1.7]; +4.0 [1.7], respectively, from baseline to month 36) following reduced injection frequency relative to the core study. At 36 months, the least-squares mean (standard error) change in the laser monotherapy group was similar to that in the ranibizumab groups (+4.1 [1.8]). Most subscale scores showed outcomes similar to that for the composite score. The greatest NEI VFQ-25 gains were consistently observed in participants for whom the study eye was the better-seeing eye.Limitations: Patients entering the extension were not randomized, and 21% of the core study participants did not enter the extension, which may have affected the results.Conclusions: Gains in patient-reported visual function at month 12 among eyes receiving ranibizumab in the core study decreased slightly by 36 months. Eyes originally receiving laser monotherapy for 12 months then ranibizumab for 24 months achieved similar gains by 36 months to eyes receiving ranibizumab for 36 months.Trial Registration: ClinicalTrials.gov: NCT00687804 and NCT00906464. [ABSTRACT FROM AUTHOR]

Diabetic macular edema is a leading cause of vision impairment among people within the working- age population. This review discusses the pathogenesis of diabetic macular edema and the treatment options currently available for the treatment of diabetic macular edema, including for focal/grid photocoagulation, intravitreal corticosteroids and intravitreal antivascular endothelial growth factor agents. The biologic rationale for novel therapeutic agents, many of which are currently being evaluated in clinical trials, also is reviewed. [ABSTRACT FROM AUTHOR]

Purpose: To assess the reproducibility of the evaluation of color photographs and fluorescein angiograms of the macula of each eye for patients enrolled in the Macular Photocoagulation Study (MPS) trials of laser photocoagulation of subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration. Methods: A total of 65 pre-enrollment and 26 posttreatment sets of photographs were regraded. The two gradings were compared on selected items judged to be of primary importance with respect to the role of the MPS Reading Center. Results: Agreement on eligibility of the neovascular lesion for an MPS trial was 88% (kappa statistic = 0.59); agreement on the size of the lesion was 86% (kappa statistic = 0.80); agreement on whether the lesion was covered by heavy treatment was 69% (kappa statistic = 0.35); and agreement on whether the treatment was in compliance with the study protocol was 73% (kappa statistic = 0.06). Conclusions: Interpretation of photographs of eyes with CNV secondary to age-related macular degeneration for eligibility and size of the lesion was reproducible in the MPS. However, adequacy of laser photocoagulation treatment could not be determined reliably from photographs. [ABSTRACT FROM AUTHOR]

Objective To compare the treatment effect and safety of photodynamic therapy with verteporfin using a standard (SF) or reduced (RF) light fluence rate with that of placebo therapy in patients with subfoveal minimally classic choroidal neovascularization (CNV) with age-related macular degeneration. Design Phase 2, multicenter, double-masked, placebo-controlled, randomized clinical trial. Setting Nineteen ophthalmology practices in North America and Europe. Participants Patients with initial best-corrected visual acuity of at least 20/250 and a lesion size of no greater than 6 Macular Photocoagulation Study (MPS) disc areas. Methods We randomly assigned 117 patients (1:1:1) to verteporfin infusion (6 mg/m2) and light application with an RF rate (300 mW/cm2) for 83 seconds (light dose of 25 J/cm2) or an SF rate (600 mW/cm2) for 83 seconds (light dose of 50 J/cm2) or to placebo infusion with RF or SF. Treatment was repeated every 3 months if the treating physician noted fluorescein leakage from CNV on angiography. Patients in whom a predominantly classic lesion developed could receive open-label standard verteporfin treatment. Best-corrected visual acuity was measured every 3 months, and angiographic changes were assessed by the Photograph Reading Center through the 3-month examination unless an ocular adverse event or conversion to a predominantly classic lesion was identified by an investigator. Safety was assessed throughout the study. All outcomes were on an intent-to-treat basis. Results One hundred three (88%) of 117 patients completed the 24-month examination. Twelve (30%) of 40 patients assigned to placebo received open-label standard verteporfin treatment after confirmation of presence of predominantly classic CNV. At month 12, a loss of at least 3 lines of visual acuity occurred in 5 (14%) of 36 eyes assigned to RF and 10 (28%) of 36 eyes assigned to SF, compared with 18 (47%) of 38 eyes assigned to placebo (RF, P = .002; SF, P = .08; RF + SF, P = .004). At month 24, this loss occurred in 9 (26%) of 34 eyes assigned to RF and 17 (53%) of 32 assigned to SF, compared with 23 (62%) of 37 eyes assigned to placebo (RF, P = .003; SF, P = .45; RF + SF, P = .03). Progression to predominantly classic CNV by 24 months was more common in the placebo group (11 [28%] of 39 patients compared with 2 [5%] of 38 in the RF group [P = .007] and 1 [3%] of 37 in the SF group [P = .002]). No unexpected ocular or systemic adverse events were identified. Treatment-related, usually transient visual disturbances were 13% with SF, 10% with placebo, and 5% with RF. Conclusions Verteporfin therapy safely reduced the risks of losing at least 15 letters (≥3 lines) of visual acuity and progression to predominantly classic CNV for at least 2 years in individuals with subfoveal minimally classic lesions due to age-related macular degeneration measuring 6 MPS disc areas or less. Based on the overall evidence available on verteporfin therapy for these lesions, the VIM Study Group would consider recommending verteporfin therapy for relatively small minimally classic lesions similar to those enrolled in the VIM Trial. [ABSTRACT FROM AUTHOR]

Purpose: To describe methods and results and to assess the value of a Traveling Vision Examiner (TVE) Program designed to provide masked vision measurements by expert vision examiners who were independent of, and traveled to, local clinical centers. Methods: The Submacular Surgery Trials (S SI) Pilot Study was conducted to refine the design and methods for a set of multicenter, randomized clinical trials to evaluate submacular surgery in patients with subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) or ocular histoplasmosis (OHS), or idiopathic CNV in which the primary study outcome would be change in 2-year best-corrected vision from baseline. As part of the SST Pilot Study, the feasibility and value of a TVE Program was assessed. The goal of the program was to obtain unbiased vision measurements, according to a standard protocol, of best-corrected visual acuity, reading speed, and contrast threshold, of each patient at 2 and 4 years after enrollment. Results: Eighty-three visits by TVEs were made to 16 centers participating in the SST Pilot Study; 239 patients had at least one masked vision examination. Comparison of pairs of vision measurements of the traveling vision examiners and local vision examiners for 71 patients made on the same day showed good agreement overall (ICC > 0.81). Conclusions: The proposed TVE Program was judged to be a feasible and useful method of providing standardized, unbiased, masked vision measurements. This approach was incorporated into the larger clinical trials conducted by the SST Research Group. [ABSTRACT FROM AUTHOR]

Objective: To estimate the relative contributions of central vision loss and general health to vision-targeted quality of life as measured by the National Eye Institute Visual Function Questionnaire (NEI-VFQ). Methods: Data on quality of life (NEI-VFQ and the 36-Item Short-Form Health Survey [SF-36]) and visual acuity were collected as part of the Submacular Surgery Trials Pilot Study. Information on medical conditions was collected by patient chart review. Twenty-four-month data for 120 patients were analyzed using linear regression methods. Results: Median patient age at the 24-month examination was 77 years; 60% were women, and 98% were non-Hispanic whites. A 3-line decrement in visual acuity in the better-seeing eye was associated with a 5.1- to 17.1- point decrement in NI 1-VI Q scores after adjustment for general health (SF-36 physical component summary [Pcs] and mental component summary [Mcs] scores). A 10-point decrement in the PCS score was associated with a 4- to 9-point decrement in NEI-VFQ scores after adjustment for visual acuity in the better-seeing eye and MCS score. A 10-point decrement in the MCS score was associated with a 4- to 8-point decrement in NI1-VFQ scores after adjustment for visual acuity in the better-seeing eye and PCS score. Diabetes, arthritis/rheumatism, and hypertension also had large effects on NEI-VFQ scores in the adjusted analysis. Conclusion.: The NEI-VFQ is sensitive to differences in visual acuity in the better-seeing eye, as expected, and to differences in general health. Adjustment for general health should be considered when comparing NEI-VFQ scores between patient groups. [ABSTRACT FROM AUTHOR]

Objective: To determine if there is a rationale for monitoring patients with age-related macular degeneration who have a minimally classic subfoveal choroidal neovascular lesion and do not receive treatment at initial examination. Methods: Participants assigned to placebo who had a minimally classic lesion composition at baseline were identified from the TAP Investigation. Fluorescein angiograms at baseline and follow-up examinations from these participants were reviewed by photograph reading center graders to determine if any follow-up angiograms had converted from a minimally classic lesion composition to a predominantly classic lesion composition. Main Outcome Measures: Proportion of minimally classic lesions at baseline that converted to a predominantly classic lesion composition, time of this conversion, and visual acuity and lesion size at the time of conversion. Results: Of the 207 patients assigned to placebo in the TAP Investigation, 98 were judged to have a minimally classic lesion at baseline in the study eye when the fluorescein angiograms were reviewed in 2001. Of these 98 patients, 39 (40%) had lesions that converted to a predominantly classic lesion composition, including 21 by the month 3 examination. At the time of conversion, 32 (82%) lesions were no greater than 9 disc areas, including 20 (51%) with visual acuity of 20/200 or better. Conclusions: These data would suggest that patients with minimally classic lesions, in whom no therapy is recommended initially, should be monitored so that potential conversion to a predominantly classic lesion can be identified promptly and verteporfin therapy considered. [ABSTRACT FROM AUTHOR]

Objective: To estimate the potential public health impact of the findings of the Age-Related Eye Disease Study (AREDS) on reducing the number of persons developing advanced age-related macular degeneration (AMD) during the next 5 years in the United States. Methods: The AREDS clinical trial provides estimates of AMD progression rates and of reduction in risk of developing advanced AMD when a high-dose nutritional supplement of antioxidants and zinc is used. These results are applied to estimates of the US population at risk, to estimate the number of people who would potentially avoid advanced AMD during 5 years if those at risk were to take a supplement such as that used in AREDS. Results: An estimated 8 million persons at least 55 years old in the United States have monocular or binocular intermediate AMD or monocular advanced AMD. They are considered to be at high risk for advanced AMD and are those for whom the AREDS formulation should be considered. Of these people, 1.3 million would develop advanced AMD if no treatment were given to reduce their risk. If all of these people at risk received supplements such as those used in AREDS, more than 300 000 (95% confidence interval, 158 000-487 000) of them would avoid advanced AMD and any associated vision loss during the next 5 years. Conclusion: If people at high risk for advanced AMD received supplements such as those suggested by AREDS results, the potential impact on public health in the United States would be considerable during the next 5 years. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate safety and short-term visual acuity and fluorescein angiographic effects of photodynamic therapy (PDT) after retreatments with verteporfin for choroidal neovascularization (CNV) in agerelated macular degeneration (AMD) that demonstrated fluorescein leakage after at least 1 course of PDT. Design: Nonrandomized, multicenter, open-label phase 1 and 2 clinical trial using 2 different retreatment dosage regimens. Setting: Four ophthalmic centers in Europe and North America providing retinal care. Methods: Standardized protocol refraction, visual acuity testing, ophthalmic examinations, color photographs, and fluorescein angiograms were used to evaluate the results of multiple PDT treatments. Two regimens (regimens 2 and 4) for treatment and retreatment were chosen from 5 used in a single-treatment study. Both regimens used a verteporfin dose of 6 mg/m² infused for 10 minutes. However, regimen 2 used a light dose of 100 J/cm² applied 20 minutes after the start of the verteporfin infusion, whereas regimen 4 used a light dose of 50, 75, or 100 J/cm² applied 15 minutes after infusion commenced. Posttreatment evaluations were planned in 31 participants up to 3 months after up to 2 retreatments given at 2- or 4-week intervals after initial PDT treatment. Similar posttreatment evaluations were planned after retreatments in 5 additional participants who were reenrolled some time more than 12 weeks after an initial PDT treatment. the initial treatment and a follow-up examination 16 to 20 weeks after the initial treatment was 0.2 lines (range, -4 to 4 lines) in regimen 2 and -1.0 line (range, -5 to 3 lines) in regimen 4. Similar outcomes were noted in the 5 reenrolled participants. Cessation of fluorescein leakage from classic CNV for at least 1 to 4 weeks could be achieved without loss of visual acuity after at least 2 treatments in 2 (6.5%) of 31 patients. Similar to single-treatment effects, the disappearance of leakage was documented... [ABSTRACT FROM AUTHOR]

Objective: To evaluate the safety and short-term visual and fluorescein angiographic effects of a single photodynamic therapy treatment with verteporfin with the use of different dosage regimens in patients with choroidal neovascularization (CNV) from age-related macular degeneration. Design: Nonrandomized, multicenter, open-label, clinical trial using 5 dosage regimens. Setting: Four ophthalmic centers in North America and Europe providing retinal care. Participants: Patients with subfoveal CNV caused by age-related macular degeneration. Methods: Standardized protocol refraction, visual acuity testing, ophthalmic examination, color photographs, and fluorescein angiograms were used to evaluate the effects of a single treatment of photodynamic therapy with verteporfin. Follow-up was planned through 3 months in 97 patients and for less than 3 months in 31 other patients. Results: The mean visual acuity change (and range of change) from baseline at the follow-up examination at week 12 after a single treatment with regimens 1 through 5 was -0.2 (-3 to +2), -0.9 (-9 to +5),-1.6 (-9 to +2), +0.4 (-8 to +7), and +0.1 (-8 to +9) lines, respectively. Only the highest light dose (150 J/cm²) in regimens 2 and 3, which produced angiographic nonperfusion of neurosensory retinal vessels, caused marked vision loss. Some cessation of fluorescein leakage from CNV was achieved without loss of vision when the light dose used was less than 150J/cm². Systemic adverse events were rare. Cessation of fluorescein leakage from CNV was noted in all regimens by 1 week after photodynamic therapy. Fluorescein leakage from at least a portion of the CNV reappeared by 4 to 12 weeks after treatment in almost all cases. Progression of classic CNV beyond the area of CNV identified before treatment was noted in 42 (51%) of the 83 eyes with classic CNV followed up for 3 months after a single treatment. Eyes in which the area of any CNV leakage at 12 weeks was less than at baseline had a... [ABSTRACT FROM AUTHOR]

The article reflects on the anastomosis of retinal vessels to lesions of choroidal neovascularization, especially in age-related macular degeneration. It argues that retinal vessels may connect to subretinal neovascularization rather than to neovascularization beneath the retinal pigment epithelium. It offers information on the term retinal angiomatous proliferans.

: PurposeTo report the occurrence of large submacular hemorrhages after photodynamic therapy with verteporfin in age-related macular degeneration patients with subfoveal choroidal neovascularization (CNV) composed of occult with no classic CNV in whom the hemorrhage precluded determining if additional therapy should be given within 3 months after initiation of treatment.: DesignRetrospective, noncomparative case series.: MethodsThe records of all age-related macular degeneration patients who received verteporfin therapy for subfoveal lesions composed of occult with no classic CNV between February and July 2001 at The Wilmer Eye Institute were reviewed. Subjects who reported either having undergone a procedure to remove intraocular blood before a month 3 follow-up visit, or who had submacular hemorrhage at the month 3 visit that was severe enough to preclude determining if additional verteporfin therapy should be given were identified.: ResultsFifty-five eyes of 52 patients were reviewed. Five eyes (9% [95% confidence interval, 1.4%–16.6%]) developed submacular hemorrhage that precluded determining if additional verteporfin therapy should be given. Visual acuity 3 months after documentation of the hemorrhage decreased a median of 8.5 lines compared with pretreatment acuity.: ConclusionsEven in the absence of acute severe visual acuity decrease, submacular hemorrhage after verteporfin therapy can be associated with severe vision loss and preclude determining if additional therapy should be given. [Copyright &y& Elsevier]

Focuses on an article that appears in the "Archives of Ophthalmology" in April 2004 that discusses age-related macular degeneration and its prevalence in the United States. How age-related macular degeneration is the leading cause of blindness; Estimate of the prevalence and distribution of age-related macular degeneration by age, race/ethnicity, and gender; Indication that the prevalence will increase in less than 20 years; Assertion that age-related macular degeneration will be a major problem if efforts are not made to reduce the risk of blindness from this disease.

: PurposeTo report a case of presumed congenital hypertrophy of the retinal pigment epithelium in the fovea of an 88-year-old woman in the setting of geographic atrophy from age-related macular degeneration.: DesignObservational case report.: MethodsAn 88-year-old woman was examined.: ResultsBest-corrected visual acuity was 20/63 in the right eye and 20/50 in the left eye. Multifocal areas of geographic atrophy and large-sized drusen were seen in the maculae of both eyes. Biomicroscopic examination of the right eye showed hyperpigmentation consistent with congenital hypertrophy of the retinal pigment epithelium through the center of the macula. No prior photographic documentation of the retina was available.: ConclusionThis case suggests that foveal congenital hypertrophy of the retinal pigment epithelium may be seen in the setting of macular geographic atrophy. Although it is theoretically possible that the hyperpigmentation is reactive rather than congenital, the pigmentation is typical for congenital hypertrophy and is unlike any reactive pigmentation in our experience or described in a MEDLINE search of features of age-related macular degeneration. The case suggests that a hypertrophic process of the retinal pigment epithelium may coexist within or immediately adjacent to the anatomic boundaries of an atrophic process such as geographic atrophy from age-related macular degeneration. [Copyright &y& Elsevier]

Purpose: To discuss the current role of laser therapies in the management of retinal vascular and neovascular diseases. Design: Perspective. Methods: Laser''s role in the management of diabetic retinopathy, age-related macular degeneration, and venous occlusive disease is discussed, with emphasis on comparing laser with anti–vascular endothelial growth factor (VEGF) therapy and discussion of situations where these treatment methods can be complementary. Results: Thermal panretinal photocoagulation remains the usual practice for treatment of neovascularization in proliferative diabetic retinopathy and after venous occlusive events. Focal/grid laser still has a role for patients with macular edema resulting from diabetes or venous occlusion that is poorly responsive to anti-VEGF agents and in patients who are unable or unwilling to return for frequent injections. Focal/grid laser also is used as combination therapy with anti-VEGF agents for these indications. Focal laser can be used for extrafoveal choroidal neovascularization to avoid the treatment burden and risks of multiple injections. Photodynamic therapy may be beneficial in the treatment of central serous chorioretinopathy and idiopathic polypoidal choroidal vasculopathy and as combination therapy with anti-VEGF agents in age-related macular degeneration. Conclusions: Anti-VEGF agents are effective in preventing vision loss and improving vision in multiple diseases, including diabetic retinopathy, neovascular age-related macular degeneration, and retinal vein occlusions. Despite a substantial decrease in its use for these conditions in recent years, laser therapies continue to serve important roles in our ability to combat retinal pathologic features and will remain a pivotal component of our practices for at least the next several years. [Copyright &y& Elsevier]

Purpose: To compare fluorescein leakage from choroidal neovascularization (CNV) with signs of intraretinal or subretinal fluid on time-domain optical coherence tomography (TD-OCT) and spectral-domain optical coherence tomography (SD-OCT) in patients receiving anti-vascular endothelial growth factor (anti-VEGF) therapy for CNV caused by age-related macular degeneration (AMD). Design: Retrospective, consecutive case series. Participants: Fifty-nine eyes of 56 patients with neovascular AMD receiving anti-VEGF therapy. Methods: All patients were imaged with fluorescein angiography (FA), TD-OCT (Stratus, Carl Zeiss Meditec, Inc., Dublin, CA), and SD-OCT (Cirrus, Carl Zeiss Meditec, Inc). All images were analyzed by an experienced reading center grader masked to all clinical data. Fluorescein leakage from CNV and OCT abnormalities (presence of interstitial fluid, retinal cystoid abnormalities, and subretinal fluid) were documented for each visit. Main Outcome Measures: Agreement of OCT findings with presence or absence of fluorescein leakage from CNV. Results: For TD-OCT, the sensitivity, specificity, positive predictive value, and negative predicative value (and 95% confidence intervals) for OCT abnormalities were 59% (46–72), 63% (50–75%), 61% (49–73), and 61% (48–74), respectively. For SD-OCT, the sensitivity, specificity, positive predictive value, and negative predictive value (and 95% confidence intervals) for OCT abnormalities were 90% (82–98), 47% (34–60), 62% (49–75), and 82% (72–92), respectively. Conclusions: Spectral-domain optical coherence tomography seems more likely than TD-OCT to detect abnormalities when fluorescein leakage from CNV is detected after anti-VEGF therapy. However, SD-OCT also seems to detect abnormalities frequently in the absence of fluorescein leakage from CNV. Whether treatment decisions based on any of these modalities result in visual acuity outcomes that are similar or superior to monthly treatments without such evaluations is unknown, but this study provides information that may assist in the design of studies to evaluate the role of OCT and FA in the management of CNV. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. [Copyright &y& Elsevier]

Purpose: To review the available information on classification of diabetic macular edema (DME) as focal or diffuse.Design: Interpretive essay.Methods: Literature review and interpretation.Results: The terms focal diabetic macular edema and diffuse diabetic macular edema frequently are used without clear definitions. Published definitions often use different examination methods and often are inconsistent. Evaluating published information on the prevalence of focal and diffuse DME, the responses of focal and diffuse DME to treatments, and the importance of focal and diffuse DME in assessing prognosis is hindered because the terms are used inconsistently. A newer vocabulary may be more constructive, one that describes discrete components of the concepts such as extent and location of macular thickening, involvement of the center of the macula, quantity and pattern of lipid exudates, source of fluorescein leakage, and regional variation in macular thickening and that distinguishes these terms from the use of the term focal when describing one type of photocoagulation technique. Developing methods for assessing component variables that can be used in clinical practice and establishing reproducibility of the methods are important tasks.Conclusions: Little evidence exists that characteristics of DME described by the terms focal and diffuse help to explain variation in visual acuity or response to treatment. It is unresolved whether a concept of focal and diffuse DME will prove clinically useful despite frequent use of the terms when describing management of DME. Further studies to address the issues are needed. [ABSTRACT FROM AUTHOR]

Objective: To assess the incidence or progression of macular edema (ME) after cataract surgery in diabetic patients using optical coherence tomography (OCT) and correlating this with degree of diabetic retinopathy or other risk factors. Design: Prospective cohort study. Participants: Fifty diabetic eyes undergoing cataract surgery. Methods: Each eye underwent 7-field fundus photography no more than 3 months before surgery. Optical coherence tomography testing was performed within 4 weeks before surgery and at 1- and 3-month postoperative visits. Best-corrected visual acuity (BCVA) was recorded at each visit. Macular edema was defined as an increase of center point thickness on OCT > 30% from preoperative baseline. Main Outcome Measures: Changes in foveal thickness and BCVA. Results: The incidence of ME on OCT was 22% (95% confidence interval, 13%–35%). The average increase in center point thickness at 1 month for eyes with ME was 202 μm, which resulted in a nearly 1-line loss of vision (0.07 logarithm of the minimum angle of resolution [logMAR] units) compared with eyes without ME gaining >2 lines of vision (0.24 logMAR units) (P>0.001). Eyes with no diabetic retinopathy developed minimal thickening of 18 μm and 14 μm at 1 and 3 months, respectively, associated with approximately 2 and 3 lines of improved vision, respectively (0.22 and 0.26 logMAR units). Eyes with moderate or severe nonproliferative diabetic retinopathy or proliferative diabetic retinopathy developed thickening of 145 μm and 131 μm at 1 and 3 months, respectively, associated with <1 and 2 lines of improved visual acuity, respectively (0.08 and 0.17 logMAR units). This difference (P = 0.05) in thickening (127 μm and 117 μm at 1 and 3 months, respectively) was correlated inversely with visual improvement (r = −0.662). Both duration of diabetes ≥ 10 years (P = 0.04) and insulin dependence (P = 0.007) were associated with reduced visual improvement. Conclusions: Diabetic eyes have a high incidence of increased center point thickness on OCT after cataract surgery, associated with a loss of vision at 1 month, with limited visual recovery at 3 months. Treatment to prevent this might improve outcomes in similar individuals after surgery. [Copyright &y& Elsevier]

Purpose: To describe in detail occurrences of acute severe visual acuity decrease after photodynamic therapy (PDT) with verteporfin in the Treatment of Age-related macular degeneration with Photodynamic therapy (TAP) Investigation and the Verteporfin In Photodynamic therapy (VIP) Trial.Design: Observational case series.Methods: Retrospective review of all cases that developed acute severe visual acuity decrease after treatment.Results: Of 15 acute severe visual acuity decrease events originally identified in 14 eyes of 14 patients, one event in one patient was judged unlikely to have been an acute severe visual acuity decrease event on retrospective review of these events in preparation of this report. Eleven events occurred after the first treatment. At follow-up, 10 improved by at least 1 line in visual acuity from the level noted at the time of the event. Of the nine patients returning for the month 24 examination, visual acuity decreased at least 3 lines from baseline in six, including at least 6 lines in four, and remained within 1 line in three. Associated abnormal morphology included three with a serous macular detachment and abnormal choroidal hypofluorescence, four with macular hemorrhage, three with a greenish subfoveal hemorrhage, and four with no abnormality. Events appeared to be more likely when patients had a visual acuity of 20/50 or better.Conclusions: Acute severe visual acuity decrease after PDT with verteporfin was an uncommon event; the risk did not outweigh the benefits of therapy previously reported. When considering verteporfin therapy, patients should be warned of the possibility of this serious adverse event. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether differences in baseline lesion size and visual acuity might explain differing results found in three different lesion compositions (predominantly classic, minimally classic, and occult with no classic) among three placebo-controlled, randomized clinical trials evaluating photodynamic therapy with verteporfin (Visudyne, Novartis AG), also termed verteporfin therapy, in patients with subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD).Methods: Exploratory analyses were conducted in patients with predominantly classic or minimally classic lesions at enrollment in the Treatment of AMD with Photodynamic Therapy (TAP) Investigation and in AMD patients with occult with no classic CNV in the Verteporfin In Photodynamic Therapy (VIP) Trial. Baseline characteristics of patients among these three lesion compositions were compared. In addition, multiple linear regression modeling was used to explore the effect of baseline lesion size, visual acuity, and lesion composition on mean change in visual acuity from baseline to 24 months.Results: At baseline, the mean size of predominantly classic lesions (3.4 disk areas) was smaller than that of minimally classic (4.7 disk areas) and occult with no classic lesions (4.3 disk areas). In the multiple linear regression model of individual lesion compositions, there was a significant treatment-by-lesion-size interaction for minimally classic and occult with no classic lesions, but not for predominantly classic lesions. Interaction between treatment and baseline visual acuity was not significant for any lesion composition. Small verteporfin-treated lesions lost less vision than large verteporfin-treated lesions in each lesion composition. In the multiple linear regression model that included all lesion compositions, lesion size was a more significant predictive factor for the magnitude of treatment benefit than either lesion composition or visual acuity. Smaller (4.0 disk areas or less) minimally classic and occult with no classic lesions had similar visual acuity outcomes to those observed in predominantly classic lesions.Conclusions: Based on exploratory analyses, lesion size in the TAP Investigation and VIP Trial was an important predictor of the magnitude of treatment benefit with verteporfin therapy in occult with no classic and minimally classic lesion compositions. In patients with AMD, treating smaller rather than larger neovascular lesions, regardless of lesion composition, likely will result in a better level of visual acuity. [ABSTRACT FROM AUTHOR]

Objective: To describe the underlying principles used to develop a web-based algorithm that incorporated intravitreal anti–vascular endothelial growth factor (anti-VEGF) treatment for diabetic macular edema (DME) in a Diabetic Retinopathy Clinical Research Network (DRCR.net) randomized clinical trial. Design: Discussion of treatment protocol for DME. Participants: Subjects with vision loss resulting from DME involving the center of the macula. Methods: The DRCR.net created an algorithm incorporating anti-VEGF injections in a comparative effectiveness randomized clinical trial evaluating intravitreal ranibizumab with prompt or deferred (≥24 weeks) focal/grid laser treatment in eyes with vision loss resulting from center-involved DME. Results confirmed that intravitreal ranibizumab with prompt or deferred laser provides superior visual acuity outcomes compared with prompt laser alone through at least 2 years. Duplication of this algorithm may not be practical for clinical practice. To share their opinion on how ophthalmologists might emulate the study protocol, participating DRCR.net investigators developed guidelines based on the algorithm''s underlying rationale. Main Outcome Measures: Clinical guidelines based on a DRCR.net protocol. Results: The treatment protocol required real-time feedback from a web-based data entry system for intravitreal injections, focal/grid laser treatment, and follow-up intervals. Guidance from this system indicated whether treatment was required or given at investigator discretion and when follow-up should be scheduled. Clinical treatment guidelines, based on the underlying clinical rationale of the DRCR.net protocol, include repeating treatment monthly as long as there is improvement in edema compared with the previous month or until the retina is no longer thickened. If thickening recurs or worsens after discontinuing treatment, treatment is resumed. Conclusions: Duplication of the approach used in the DRCR.net randomized clinical trial to treat DME involving the center of the macula with intravitreal ranibizumab may not be practical in clinical practice, but likely can be emulated based on an understanding of the underlying rationale for the study protocol. Inherent differences between a web-based treatment algorithm and a clinical approach may lead to differences in outcomes that are impossible to predict. The closer the clinical approach is to the algorithm used in the study, the more likely the outcomes will be similar to those published. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. [Copyright &y& Elsevier]

Purpose: To determine the sensitivity of time domain optical coherence tomography (OCT) in detecting conversion to neovascular age-related macular degeneration (AMD) in eyes at high risk for choroidal neovascularization (CNV), compared with detection using fluorescein angiography (FA) as the gold standard. Design: Prospective, multicenter, observational study. Participants: Individuals aged ≥50 years with nonneovascular AMD at high risk of progressing to CNV in the study eye and evidence of neovascular AMD in the fellow eye. Methods: At study entry and every 3 months through 2 years, participants underwent best-corrected visual acuity, supervised Amsler grid testing, preferential hyperacuity perimetry (PHP) testing, stereoscopic digital fundus photographs with FA, and OCT imaging. A central Reading Center graded all images. Main Outcomes Measures: The sensitivity of OCT in detecting conversion to neovascular AMD by 2 years, using FA as the reference standard. Secondary outcomes included comparison of sensitivity, specificity, positive predictive value, and negative predictive value of OCT, PHP, and supervised Amsler grid relative to FA for detecting incident CNV. Results: A total of 98 participants were enrolled; 87 (89%) of these individuals either completed the 24-month visit or exited the study after developing CNV. Fifteen (17%) study eyes had incident CNV confirmed on FA by the Reading Center. The sensitivity of each modality for detecting CNV was: OCT 0.40 (95% confidence interval [CI], 0.16–0.68), supervised Amsler grid 0.42 (95% CI, 0.15–0.72), and PHP 0.50 (95% CI, 0.23–0.77). Treatment for incident CNV was recommended by the study investigator in 13 study eyes. Sensitivity of the testing modalities for detection of CNV in these 13 eyes was 0.69 (95% CI, 0.39–0.91) for OCT, 0.50 (95% CI, 0.19–0.81) for supervised Amsler grid, and 0.70 (95% CI, 0.35–0.93) for PHP. Specificity of the OCT was higher than that of the Amsler grid and PHP. Conclusions: Time-domain OCT, supervised Amsler grid, and PHP have low to moderate sensitivity for detection of new-onset CNV compared with FA. Optical coherence tomography has greater specificity than Amsler grid or PHP. Among fellow eyes of individuals with unilateral CNV, FA remains the best method to detect new-onset CNV. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. [Copyright &y& Elsevier]

Objective: To show that low luminance visual dysfunction is predictive of subsequent visual acuity (VA) loss in eyes with geographic atrophy (GA) resulting from age-related macular degeneration (AMD). Design: Cohort study examining the prospective natural history study of GA from 1992 through 2000 at the Wilmer Eye Institute. Participants: Ninety-one participants with GA resulting from AMD without choroidal neovascularization in at least 1 eye who completed a 2-year study examination. Methods: Annual examinations included measurement of best-corrected VA, low luminance VA, Pelli-Robson contrast sensitivity, reading speed, examination, and fundus photography. The total GA area was quantified, as was the GA within a 10.2-mm2 circle centered on the fovea. Main Outcome Measures: Visual acuity loss at 2 years and risk factors for visual loss. Results: Participants with baseline VA of 20/50 or more had a 40% 2-year rate of VA loss of 3 lines or more, compared with 13% for the participants with worse baseline acuities. The baseline low-luminance deficit (LLD) in VA was a strong predictor of subsequent VA loss for all levels of baseline VA. Within the good baseline VA group, the relative risk (RR) of 3-line loss for the worse LLD group compared with the better LLD group was 2.88 (95% confidence interval [CI], 1.13–7.35). The LLD is a stable and reproducible measure. Other significant visual function predictors of subsequent VA loss in eyes with good baseline VA included foveal dark-adapted sensitivity (RR, 4.20; 95% CI, 1.39–12.71) and reduced reading rate (RR, 2.43; 95% CI, 1.11–5.31). The rate of VA loss within the good acuity group was higher when the GA included 25% to 75% of the central 10.2 mm2 than in eyes with GA including less than 25% or more than 75% of the central 10.2 mm2. The following were not significant predictors of subsequent VA loss among these participants: age, gender, fellow eye diagnosis, fellow eye VA, baseline GA area, and GA enlargement rate. Conclusions: Visual function measures can predict the risk of future VA loss in subjects with GA and good baseline VA. They may allow identification of the highest risk group for VA loss, enabling more efficient design of clinical trials. They also may be appropriate surrogate measures of foveal health in short-term treatment trials. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article. [Copyright &y& Elsevier]

Objective: To describe micronutrient usage patterns among patients at a tertiary ophthalmic center. Design: Cross-sectional clinical case series. Participants: Three hundred thirty-two adult patients with a diagnosis of age-related macular degeneration (AMD). Methods: Participants were surveyed about micronutrient usage patterns. The treating ophthalmologist recorded AMD severity using the Age-Related Eye Disease Study (AREDS) classification system. Main Outcome Measures: Responses to study questionnaire and level of AMD severity. Results: Among 332 participants, 309 (93%) were using supplements, among which 174 (52%) supplemented with an AREDS-like formulation. Of these 174, 140 (80%) were considered AREDS supplement candidates based on study guidelines. Applying AREDS supplementation guidelines to the full cohort, 228 (69%) were candidates for supplementation. Only 140 (61%) of these individuals were confirmed to be using the correct formulation and dosage; an additional 13 (6%) used the AREDS formulation but were not using the recommended dosage. Conclusions: Among patients receiving care for AMD at a tertiary retinal center, more than one third of those deemed candidates for AREDS-type supplements were not using them or were using an incorrect dose. Furthermore, nearly one fifth of participants who were using high-dose supplements did not have a level of AMD anticipated to benefit from usage. Increased patient education is needed regarding the recommendations of AREDS. [Copyright &y& Elsevier]

Purpose: To report the enlargement rate of geographic atrophy (GA) over time, its relationship to size of atrophy at baseline and to prior enlargement rate, and the implications for designing future treatment trials for GA. Design: Prospective natural history study of GA resulting from age-related macular degeneration. Participants: Two hundred twelve eyes of 131 patients were included in the analysis. Methods: Annual follow-up included stereo color fundus photographs. The areas of GA were identified and measured, and the rate of enlargement of the atrophy was assessed. Sample sizes for clinical trials using systemic treatment and uniocular treatment were determined. Main Outcome Measure: Rate of enlargement of the atrophy. Results: The median overall enlargement rate was 2.1 mm2/year (mean, 2.6 mm2/year). Eyes with larger areas of atrophy at baseline tended to have larger enlargement rates, but knowledge of prior rates of enlargement was the most significant factor in predicting subsequent enlargement rates. There was high concordance between the enlargement rates in the 2 eyes of patients with bilateral GA (correlation coefficient, 0.76). To detect a 25% reduction in enlargement rate for a systemic treatment (α, 0.05; power, 0.80; losses to follow-up, 15%), 153 patients each in a control and treatment group would be required for a trial with a 2-year follow-up period for each patient. For a uniocular treatment, 38 patients with bilateral GA would be required, with the untreated eye serving as a control for the treated eye. Conclusions: Treatment trials for GA with an outcome variable of change in enlargement rate are feasible. [Copyright &y& Elsevier]