Four-Year Visual Outcomes in the Protocol W Randomized Trial of Intravitreous Aflibercept for Prevention of Vision-Threatening Complications of Diabetic Retinopathy.

Importance: Anti-vascular endothelial growth factor (VEGF) injections in eyes with nonproliferative diabetic retinopathy (NPDR) without center-involved diabetic macular edema (CI-DME) reduce development of vision-threatening complications from diabetes over at least 2 years, but whether this treatment has a longer-term benefit on visual acuity is unknown. Objective: To compare the primary 4-year outcomes of visual acuity and rates of vision-threatening complications in eyes with moderate to severe NPDR treated with intravitreal aflibercept compared with sham. The primary 2-year analysis of this study has been reported. Design, Setting, and Participants: Randomized clinical trial conducted at 64 clinical sites in the US and Canada from January 2016 to March 2018, enrolling 328 adults (399 eyes) with moderate to severe NPDR (Early Treatment Diabetic Retinopathy Study [ETDRS] severity level 43-53; range, 0 [worst] to 100 [best]) without CI-DME. Interventions: Eyes were randomly assigned to 2.0 mg aflibercept (n = 200) or sham (n = 199). Eight injections were administered at defined intervals through 2 years, continuing quarterly through 4 years unless the eye improved to mild NPDR or better. Aflibercept was given in both groups to treat development of high-risk proliferative diabetic retinopathy (PDR) or CI-DME with vision loss. Main Outcomes and Measures: Development of PDR or CI-DME with vision loss (≥10 letters at 1 visit or ≥5 letters at 2 consecutive visits) and change in visual acuity (best corrected ETDRS letter score) from baseline to 4 years. Results: Among participants (mean age 56 years; 42.4% female; 5% Asian, 15% Black, 32% Hispanic, 45% White), the 4-year cumulative probability of developing PDR or CI-DME with vision loss was 33.9% with aflibercept vs 56.9% with sham (adjusted hazard ratio, 0.40 [97.5% CI, 0.28 to 0.57]; P < .001). The mean (SD) change in visual acuity from baseline to 4 years was -2.7 (6.5) letters with aflibercept and -2.4 (5.8) letters with sham (adjusted mean difference, -0.5 letters [97.5% CI, -2.3 to 1.3]; P = .52). Antiplatelet Trialists' Collaboration cardiovascular/cerebrovascular event rates were 9.9% (7 of 71) in bilateral participants, 10.9% (14 of 129) in unilateral aflibercept participants, and 7.8% (10 of 128) in unilateral sham participants. Conclusions and Relevance: Among patients with NPDR but without CI-DME at 4 years treatment with aflibercept vs sham, initiating aflibercept treatment only if vision-threatening complications developed, resulted in statistically significant anatomic improvement but no improvement in visual acuity. Aflibercept as a preventive strategy, as used in this trial, may not be generally warranted for patients with NPDR without CI-DME. Trial Registration: ClinicalTrials.gov Identifier: NCT02634333.

Effect of Intravitreous Aflibercept vs Vitrectomy With Panretinal Photocoagulation on Visual Acuity in Patients With Vitreous Hemorrhage From Proliferative Diabetic Retinopathy: A Randomized Clinical Trial.

Importance: Vitreous hemorrhage from proliferative diabetic retinopathy can cause loss of vision. The best management approach is unknown. Objective: To compare initial treatment with intravitreous aflibercept vs vitrectomy with panretinal photocoagulation for vitreous hemorrhage from proliferative diabetic retinopathy. Design, Setting, and Participants: Randomized clinical trial at 39 DRCR Retina Network sites in the US and Canada including 205 adults with vison loss due to vitreous hemorrhage from proliferative diabetic retinopathy who were enrolled from November 2016 to December 2017. The final follow-up visit was completed in January 2020. Interventions: Random assignment of eyes (1 per participant) to aflibercept (100 participants) or vitrectomy with panretinal photocoagulation (105 participants). Participants whose eyes were assigned to aflibercept initially received 4 monthly injections. Both groups could receive aflibercept or vitrectomy during follow-up based on protocol criteria. Main Outcomes and Measures: The primary outcome was mean visual acuity letter score (range, 0-100; higher scores indicate better vision) over 24 weeks (area under the curve); the study was powered to detect a difference of 8 letters. Secondary outcomes included mean visual acuity at 4 weeks and 2 years. Results: Among 205 participants (205 eyes) who were randomized (mean [SD] age, 57 [11] years; 115 [56%] men; mean visual acuity letter score, 34.5 [Snellen equivalent, 20/200]), 95% (195 of 205) completed the 24-week visit and 90% (177 of 196, excluding 9 deaths) completed the 2-year visit. The mean visual acuity letter score over 24 weeks was 59.3 (Snellen equivalent, 20/63) (95% CI, 54.9 to 63.7) in the aflibercept group vs 63.0 (Snellen equivalent, 20/63) (95% CI, 58.6 to 67.3) in the vitrectomy group (adjusted difference, -5.0 [95% CI, -10.2 to 0.3], P = .06). Among 23 secondary outcomes, 15 showed no significant difference. The mean visual acuity letter score was 52.6 (Snellen equivalent, 20/100) in the aflibercept group vs 62.3 (Snellen equivalent, 20/63) in the vitrectomy group at 4 weeks (adjusted difference, -11.2 [95% CI, -18.5 to -3.9], P = .003) and 73.7 (Snellen equivalent, 20/40) vs 71.0 (Snellen equivalent, 20/40) at 2 years (adjusted difference, 2.7 [95% CI, -3.1 to 8.4], P = .36). Over 2 years, 33 eyes (33%) assigned to aflibercept received vitrectomy and 34 eyes (32%) assigned to vitrectomy received subsequent aflibercept. Conclusions and Relevance: Among participants whose eyes had vitreous hemorrhage from proliferative diabetic retinopathy, there was no statistically significant difference in the primary outcome of mean visual acuity letter score over 24 weeks following initial treatment with intravitreous aflibercept vs vitrectomy with panretinal photocoagulation. However, the study may have been underpowered, considering the range of the 95% CI, to detect a clinically important benefit in favor of initial vitrectomy with panretinal photocoagulation. Trial Registration: ClinicalTrials.gov Identifier: NCT02858076.

Early treatment response of fluocinolone (retisert) implantation in patients with uveitic macular edema: an optical coherence tomography study.

PURPOSE: To analyze the early spectral domain optical coherence tomography changes after fluocinolone implantation in eyes with baseline uveitic macular edema. METHODS: Patients with uveitic macular edema and who received fluocinolone implantations by 2 surgeons (R.P.S. and J.E.S.) at the Cole Eye Institute (Cleveland Clinic, Cleveland, OH) from September 2009 to July 2010 were eligible for this study. Best-corrected visual acuity, intraocular pressure, central subfield thickness, cube volume, cube average thickness, and cystoid macular edema grade were recorded before implantation and in the early postoperative period (median: 3 months postimplantation). Changes in these variables were analyzed using the Wilcoxon signed-rank test for paired comparisons of clustered data. P values were 2 sided, and alpha was set at 0.05. RESULTS: Twelve eyes of seven patients were included in the study. The median best-corrected visual acuity improved in the early postoperative period after implantation (20/80 before implantation and 20/50 after implantation), but this improvement was not found to be significant (P = 0.12). However, the spectral domain optical coherence tomography measurements-central subfield thickness, cube volume, cube average thickness, and cystoid macular edema grade-were all significantly reduced (median changes: -234 µm [P = 0.02], -1 mm [P = 0.04], -39 µm [P = 0.04], and -3 [P = 0.03], respectively). CONCLUSION: Fluocinolone implantation is associated with a significant reduction in macular edema as measured by spectral domain optical coherence tomography in the early postoperative period, a result that is consistent with the proposed mechanism of the drug.

Vogt-Koyanagi-Harada-like Syndrome Induced by Checkpoint Inhibitor Cemiplimab.

Checkpoint inhibition targeting programmed cell-death protein 1 has demonstrated efficacy for a wide range of indications including cutaneous malignancy. However, immune-related adverse events (irAEs), including infrequent but visually impactful ocular irAEs, require careful consideration of treatment options, including medication withdrawal, local corticosteroids, or rarely immunomodulation. This case presents a 53-year-old woman who developed uveitis and mucous membrane ulcers after treatment for numerous cutaneous neoplasms, primarily squamous cell carcinoma, with the programmed cell-death protein 1 inhibitor cemiplimab. Ophthalmic examination revealed diffuse choroidal depigmentation consistent with a Vogt-Koyanagi-Harada-like syndrome. Topical and periocular steroids were used to treat the intraocular inflammation, and cemiplimab was discontinued. Because of ongoing severe uveitis, systemic corticosteroids and corticosteroid-sparing immunosuppression were initiated. Specifically, azathioprine and methotrexate were introduced, but each was stopped due to side effects, prompting the initiation of adalimumab (ADA) treatment. While ADA controlled intraocular inflammation, the squamous cell carcinomas were noted to progress, resulting in the discontinuation of ADA. However, a uveitis recurrence was observed. After a discussion of risks and benefits of biologic immunosuppressive therapy, including the risk of vision loss, ADA was restarted with successful disease quiescence at a 16-month follow-up. The cutaneous neoplasms were managed with topical and intralesional therapies, such as 5-fluorouracil. Recent dermatologic examinations suggested no new cutaneous lesions. This scenario presents the effective use of ADA in an ocular irAE that balances the management of sight-threatening ocular inflammation with the risk of promoting recurrent or de novo neoplastic disease.

Effect of Intravitreous Anti-Vascular Endothelial Growth Factor vs Sham Treatment for Prevention of Vision-Threatening Complications of Diabetic Retinopathy: The Protocol W Randomized Clinical Trial.

IMPORTANCE: The role of anti-vascular endothelial growth factor injections for the management of nonproliferative diabetic retinopathy (NPDR) without center-involved diabetic macular edema (CI-DME) has not been clearly established. OBJECTIVE: To determine the efficacy of intravitreous aflibercept injections compared with sham treatment in preventing potentially vision-threatening complications in eyes with moderate to severe NPDR. DESIGN, SETTING, AND PARTICIPANTS: Data for this study were collected between January 15, 2016, and May 28, 2020, from the ongoing DRCR Retina Network Protocol W randomized clinical trial, conducted at 64 US and Canadian sites among 328 adults (399 eyes) with moderate to severe NPDR (Early Treatment Diabetic Retinopathy Study severity level, 43-53), without CI-DME. Analyses followed the intent-to-treat principle. INTERVENTIONS: Eyes were randomly assigned to 2.0 mg of aflibercept injections (n = 200) or sham (n = 199) given at baseline; 1, 2, and 4 months; and every 4 months through 2 years. Between 2 and 4 years, treatment was deferred if the eye had mild NPDR or better. Aflibercept was administered in both groups if CI-DME with vision loss (≥10 letters at 1 visit or 5-9 letters at 2 consecutive visits) or high-risk proliferative diabetic retinopathy (PDR) developed. MAIN OUTCOMES AND MEASURES: Development of CI-DME with vision loss or PDR through May 2020, when the last 2-year visit was completed. RESULTS: Among the 328 participants (57.6% men [230 of 399 eyes]; mean [SD] age, 56 [11] years), the 2-year cumulative probability of developing CI-DME with vision loss or PDR was 16.3% with aflibercept vs 43.5% with sham. The overall hazard ratio for either outcome was 0.32 (97.5% CI, 0.21-0.50; P < .001), favoring aflibercept. The 2-year cumulative probability of developing PDR was 13.5% in the aflibercept group vs 33.2% in the sham group, and the 2-year cumulative probability of developing CI-DME with vision loss was 4.1% in the aflibercept group vs 14.8% in the sham group. The mean (SD) change in visual acuity from baseline to 2 years was -0.9 (5.8) letters with aflibercept and -2.0 (6.1) letters with sham (adjusted mean difference, 0.5 letters [97.5% CI, -1.0 to 1.9 letters]; P = .47). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, among eyes with moderate to severe NPDR, the proportion of eyes that developed PDR or vision-reducing CI-DME was lower with periodic aflibercept compared with sham treatment. However, through 2 years, preventive treatment did not confer visual acuity benefit compared with observation plus treatment with aflibercept only after development of PDR or vision-reducing CI-DME. The 4-year results will be important to assess longer-term visual acuity outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02634333.

Assessment of the DRCR Retina Network Approach to Management With Initial Observation for Eyes With Center-Involved Diabetic Macular Edema and Good Visual Acuity: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Among eyes with center-involved diabetic macular edema (CI-DME) and good visual acuity (VA), randomized clinical trial results showed no difference in VA loss between initial observation plus aflibercept only if VA decreased, initial focal/grid laser plus aflibercept only if VA decreased, or prompt aflibercept. Understanding the initial observation approach is relevant to patient management. Objective: To assess the DRCR Retina Network protocol-defined approach and outcomes of initial observation with aflibercept only if VA worsened. Design, Setting, and Participants: This was a post hoc secondary analyses of a randomized clinical trial of the DRCR Retina Network Protocol V that included 91 US and Canadian sites from November 2013 to September 2018. Participants were adults (n = 236) with type 1 or 2 diabetes, 1 study eye with CI-DME, and VA letter score at least 79 (Snellen equivalent, 20/25 or better) assigned to initial observation. Data were analyzed from March 2019 to November 2019. Interventions: Initial observation and follow-up with aflibercept only for VA loss of at least 10 letters from baseline at 1 visit or 5 to 9 letters at 2 consecutive visits. Follow-up occurred at 8 weeks and then every 16 weeks unless VA or optical coherence tomography central subfield thickness worsened. Main Outcomes and Measures: Whether individuals received aflibercept. Results: Among 236 eyes in 236 individuals (149 [63%] male; median age, 60 years [interquartile range, 53-67 years]) randomly assigned to initial observation, 80 (34%) were treated with aflibercept during 2 years of follow-up. At 2 years, the median VA letter score was 86.0 (interquartile range, 89.0-81.0; median Snellen equivalent, 20/20 [20/16-20/25]). Receipt of aflibercept was more likely in eyes with baseline central subfield thickness at least 300 µm (Zeiss-Stratus equivalent) vs less than 300 µm (45% vs 26%; hazard ratio [HR], 1.98 [95% CI, 1.26-3.13], continuous P = .005), moderately severe nonproliferative diabetic retinopathy (Early Treatment Diabetic Retinopathy Study retinopathy severity level 47) and above vs moderate nonproliferative diabetic retinopathy (retinopathy severity level 43) and below (51% vs 27%; HR, 2.22 [95% CI, 1.42-3.47], ordinal P < .001), and among participants whose nonstudy eye received DME treatment within 4 months of randomization vs not (52% vs 25%; HR, 2.55 [95% CI, 1.64-3.99], P < .001). Conclusions and Relevance: Most eyes managed with initial observation plus aflibercept only if VA worsened maintained good vision at 2 years and did not require aflibercept for VA loss. However, the eyes in the trial were approximately twice as likely to receive aflibercept for VA loss if they had greater baseline central subfield thickness, worse diabetic retinopathy severity level, or a nonstudy eye receiving treatment for DME. Trial Registration: ClinicalTrials.gov Identifier: NCT01909791.

Spectral domain optical coherence tomography characteristics of cuticular drusen.

PURPOSE: To evaluate the appearance of cuticular drusen with spectral domain optical coherence tomography. METHODS: Eyes of patients with cuticular drusen were imaged using a prototype spectral domain optical coherence tomography instrument with 5-microm axial resolution. Thickness maps were obtained after automated segmentation of the internal limiting membrane and retinal pigment epithelium layers using a proprietary algorithm. The volume of subretinal fluid (SRF) was calculated using a manual segmentation technique that involved drawing boundaries around the SRF. The repeatability of these measurements was tested by comparing the volume measurements from multiple scans performed on the same day in four eyes of three patients. RESULTS: Sixteen eyes from eight patients with cuticular drusen were scanned. Areas of decreased retinal thickness overlying drusen were best visualized using the three-dimensional retinal thickness map. The distribution and sawtooth pattern of cuticular drusen were best visualized using three-dimensional retinal pigment epithelium segmentation. Of the 16 eyes, 13 had SRF within the macula. In the eyes with macular SRF, characteristic excrescences were present along the outer retina and attenuation of the photoreceptor inner and outer segment boundary were observed in many areas. In areas where the retina was detached, the retinal pigment epithelium-Bruch's membrane complex appeared nodular or attenuated. The volumetric measurements of the SRF were performed using a manual segmentation with a 1.11% mean difference between repeated measurements on the same day (range, 0.47-1.68%; standard deviation, 0.55%). CONCLUSION: The sawtooth pattern of drusen and the presence of excrescences along the detached outer retina are characteristic features of cuticular drusen that should be helpful in confirming the diagnosis of this condition. The volumetric analysis of the SRF is repeatable and may be useful in following the clinical course of these patients.

"Pacman" invasion of the retina: Two cases of ophthalmomyiasis interna posterior.

PURPOSE: To discuss two striking cases of ophthalmomyiasis interna posterior, in which the larval stage of a botfly is found in the posterior segment. OBSERVATIONS: In the first case, the subretinal maggot is alive and found to be migrating under the retina. The maggot was lasered in the office and killed. In the second case, a dead maggot was discovered in the subretinal space in a child, after it had caused significant subretinal scarring and permanent vision loss. CONCLUSIONS AND IMPORTANCE: Ophthalmomyiasis is a rare condition that can often be unrecognized and result in permanent vision loss. Early diagnosis and photocoagulation of the larva (if alive) can halt progression of vision loss in these cases.

Topographic comparison of the visual function on multifocal visual evoked potentials with optic nerve structure on heidelberg retinal tomography.

PURPOSE: The authors' objective was to compare the visual field obtained using multifocal visual evoked potential (mfVEP) testing with the optic nerve parameters of Heidelberg retinal tomography (HRT; Heidelberg Engineering, Heidelberg, Germany; software version 2.01) in primary open-angle glaucoma (POAG) patients and normal controls and to determine which parameters correlate with visual function. DESIGN: Cross-sectional study. PARTICIPANTS: Eighty-one eyes of 42 adult POAG patients and normal controls between the ages of 40 and 80 years, of which 35 patients (67 eyes; mean age+/-standard deviation [SD], 68+/-10 years) had POAG, and 7 individuals who served as normal controls (14 eyes; mean age+/-SD, 61+/-10 years) were included. METHODS: A monocular mfVEP test, the AccuMap (Opera software version 2.0; ObjectiVision Pty. Ltd., Sydney, Australia), with a 58-sector pattern-reversal dart board array was recorded in both eyes per patient. These patients underwent the HRT 2 and mfVEP tests within 3 months of each other. MAIN OUTCOME MEASURES: Amplitudes in the superior hemisphere of the mfVEP trace were compared with the HRT parameters in the inferior hemisphere of the HRT and vice versa using mixed effects regression models. RESULTS: Amplitudes on the superior hemisphere of the mfVEP recordings showed a significant direct correlation with rim-to-disc area ratio (P = 0.0037), rim volume (P = 0.0421), and mean retinal nerve fiber layer (RNFL) thickness (P = 0.0016) and a significant inverse correlation with cup area (P = 0.0009) and cup-to-disc area ratio (P = 0.0037) in the inferior hemisphere of the HRT results. Amplitudes on the inferior hemisphere showed a significant direct correlation with rim-to-disc area ratio (P = 0.036) and a significant inverse correlation with cup area (P = 0.0007), cup-to-disc area ratio (P = 0.036), cup volume (P<0.0001), and mean cup depth (P = 0.0012) in the superior hemisphere of the HRT results. CONCLUSIONS: Results from mfVEP and HRT showed correlation between visual function and optic nerve structure.

Three-dimensional spectral-domain optical coherence tomography images of the retina in the presence of epiretinal membranes.

PURPOSE: To study the inner surface of the retina in the presence of epiretinal membranes (ERMs) using a prototype spectral-domain optical coherence tomography (SD-OCT) device. DESIGN: Small case series, performed in the Department of Ophthalmology, Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, from August 2005 through December 2006. METHOD: An 8-microm axial-resolution SD-OCT instrument was used to scan the eyes of patients diagnosed with ERM. The ERM and the internal limiting membrane (ILM) were segmented separately to evaluate the traction caused by the ERM on the retina. It was then possible to reconstruct the ILM and ERM surfaces in 3-dimensional space and to obtain corresponding retinal thickness maps. RESULTS: SD-OCT B scans showed the points of attachment of the ERM to the ILM. Segmented surface maps of the ERM produced very smooth sheets, whereas those of the ILM presented wrinkles under and around the ERM. CONCLUSIONS: SD-OCT revealed the geometry of retinal traction in eyes with ERM and may be useful in understanding further the pathologic features of these lesions.

Macular thickness measurements in normal eyes using spectral domain optical coherence tomography.

BACKGROUND AND OBJECTIVE: Knowledge of the macular thickness in a normal population is important for the evaluation of pathological macular change. The purpose of this study was to define and measure macular thickness in normal eyes using spectral domain optical coherence tomography (OCT). PATIENTS AND METHODS: Fifty eyes from 50 normal subjects (29 men and 21 women, aged 22 to 68 years) were scanned with a prototype Cirrus HD-OCT system (5 microm axial resolution) (Carl Zeiss Meditec, Inc.). The proprietary Cirrus segmentation algorithm was used to produce retinal thickness maps, which were then averaged over 9 regions defined by a circular target centered at the true fovea location. The macular thickness of 13 subjects scanned with both HD-OCT and StratusOCT were compared. RESULTS: After centering the fovea, the mean and standard deviation values for retinal thickness measurements were calculated point wise and averaged on standard regions. For patients scanned with both systems, the thickness measurements from HD-OCT were approximately 50 microm larger than those from StratusOCT. The difference between the two measurements decreased somewhat with eccentricity. CONCLUSION: Using HD-OCT, it is possible to acquire retinal data sets containing an unprecedented number of data points. Furthermore, it is possible to use OCT fundus images to evaluate the scan quality and to center the measurement at the fovea. These advantages, together with good automated segmentation, can produce more accurate retinal thickness measurements. Incorporation of the photoreceptor layer in the measurements is anatomically meaningful and may be significant in evaluating various retinal pathologies and visual acuity outcomes.

Composite spectral domain optical coherence tomography images of diabetic tractional retinal detachment.

This article describes the spectral domain optical coherence tomography (SD-OCT) findings in three patients with diabetic tractional retinal detachment. Three patients underwent fundus photography and SD-OCT imaging before and after pars plana vitrectomy, endola-ser, and membrane peel. On SD-OCT, all three patients exhibited significant improvement or resolution of subretinal fluid after the surgical release of traction. In this case series, a clinically useful method of visualizing SD-OCT images is demonstrated. Composite images were manually constructed with commercially available software by merging high-density B-scans from the macula and optic nerve. The composite image allowed simultaneous visualization of the effects of proliferative diabetic retinopathy on the macula and optic nerve and is particularly helpful in evaluating tractional macular detachment.

Spectral domain optical coherence tomography for proliferative diabetic retinopathy with subhyaloid hemorrhage.

A prototype 6-microm axial resolution spectral domain optical coherence tomography (SD-OCT) device was used to image the retina of a patient with uncontrolled diabetes mellitus who had proliferative diabetic retinopathy with subhyaloid hemorrhage. A raster scan pattern with 128 B-scans covering a 6 X 6 X 2-mm volume of the retina was obtained. SD-OCT showed the presence of blood localized between the internal limiting membrane and the posterior hyaloid face and allowed visualization of the cross sectional retinal architecture and the vitreoretinal interface at different horizontal levels that could be registered with the color fundus photograph. SD-OCT provided useful information about the relationship of the hemorrhage to the posterior hyaloid and the retina.

Imaging serpiginous choroidopathy with spectral domain optical coherence tomography.

The use of spectral domain optical coherence tomography (SD-OCT) in the study of chronic serpiginous choroiditis was evaluated. Two patients with chronic serpiginous choroiditis were imaged using two prototype SD-OCT systems (6-microm axial resolution). Raster scans covering 6 x 6 X 2-mm regions of the retina were obtained, enabling the study of different retinal cross-sectional images. Thickness maps were obtained after segmentation of retinal layers, which could be compared with those on follow-up. SD-OCT allowed the visualization of the cross-sectional retinal architecture at different horizontal positions. Superimposition of SD-OCT generated reconstructed fundus images with fundus photographs provided accurate images registration. Segmentation of retinal layers provided thickness maps and higher-density improved visualization of photoreceptor layer, cysts, and atrophy, which was useful in following change in disease activity over time. The researchers concluded that SD-OCT is a useful tool to study disease morphology and follow-up of chronic serpiginous choroiditis.

Repeatability of the multifocal visual evoked potentials in a clinical glaucoma setting.

BACKGROUND: To determine the reproducibility of the multifocal visual evoked potentials (mfVEP) test results in a clinical glaucoma setting, and the factors that affect variability. METHODS: This was an observational case series study. The monocular mfVEP test, having a 58-sector, pattern-reversal dartboard array, was performed twice within 4 weeks in both eyes of 29 adult open-angle glaucoma (OAG) patients and suspects, using AccuMap Opera Software (ObjectiVision Pty Ltd, Sydney, Australia). The AccuMap severity index (ASI), the mean amplitude, and the individual amplitudes in each sector were compared between the 2 tests using intraclass correlations (ICCs). The effects of the severity of mfVEP field defects and signal-to-noise ratio (SNR) on the reproducibility of these variables were determined using the McNemar test and the Spearman rank correlation, respectively. RESULTS: The average ICCs of the ASI and amplitudes in the 2 tests were 0.84 and 0.87, respectively. Two sectors in the right eye and 6 in the left eye had significant differences between the 2 tests (Wilcoxon signed-rank p < 0.05). Larger differences were observed in patients having lower SNR (Spearman p = 0.022). Forty-six of the 58 eyes stayed within the same diagnosis category on repeating the test (i.e., within normal limits or outside normal limits). INTERPRETATION: Although there were some isolated examples of clinically significant differences on repeating the mfVEP test in our patients, our results suggest overall good repeat reliability. The variability of the test was higher in patients having high noise levels during the test.

Effect of Adding Dexamethasone to Continued Ranibizumab Treatment in Patients With Persistent Diabetic Macular Edema: A DRCR Network Phase 2 Randomized Clinical Trial.

Importance: Some eyes have persistent diabetic macular edema (DME) following anti-vascular endothelial growth factor (anti-VEGF) therapy for DME. Subsequently adding intravitreous corticosteroids to the treatment regimen might result in better outcomes than continued anti-VEGF therapy alone. Objective: To compare continued intravitreous ranibizumab alone with ranibizumab plus intravitreous dexamethasone implant in eyes with persistent DME. Design, Setting, and Participants: Phase 2 multicenter randomized clinical trial conducted at 40 US sites in 129 eyes from 116 adults with diabetes between February 2014 and December 2016. Eyes had persistent DME, with visual acuity of 20/32 to 20/320 after at least 3 anti-VEGF injections before a run-in phase, which included an additional 3 monthly 0.3-mg ranibizumab injections. Data analysis was according to intent to treat. Interventions: Following the run-in phase, study eyes that had persistent DME and were otherwise eligible were randomly assigned to receive 700 µg of dexamethasone (combination group, 65 eyes) or sham treatment (ranibizumab group, 64 eyes) in addition to continued 0.3-mg ranibizumab in both treatment arms as often as every 4 weeks based on a structured re-treatment protocol. Main Outcomes and Measures: The primary outcome was change in mean visual acuity letter score at 24 weeks as measured by the electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS). The principal secondary outcome was change in mean central subfield thickness as measured with the use of optical coherence tomography. Results: Of the 116 randomized patients, median age was 65 years (interquartile range [IQR], 58-71 years); 50.9% were female and 60.3% were white. Mean (SD) improvement in visual acuity from randomization was 2.7 (9.8) letters in the combination group and 3.0 (7.1) letters in the ranibizumab group, with the adjusted treatment group difference (combination minus ranibizumab) of -0.5 letters (95% CI, -3.6 to 2.5; 2-sided P = .73). Mean (SD) change in central subfield thickness in the combination group was -110 (86) µm compared with -62 (97) µm for the ranibizumab group (adjusted difference, -52; 95% CI, -82 to -22; 2-sided P < .001). Nineteen eyes (29%) in the combination group experienced increased intraocular pressure or initiated treatment with antihypertensive eyedrops compared with 0 in the ranibizumab group (2-sided P < .001). Conclusions and Relevance: Although its use is more likely to reduce retinal thickness and increase intraocular pressure, the addition of intravitreous dexamethasone to continued ranibizumab therapy does not improve visual acuity at 24 weeks more than continued ranibizumab therapy alone among eyes with persistent DME following anti-VEGF therapy. Trial Registration: clinicaltrials.gov Identifier: NCT01945866.

Does treated systemic hypertension affect progression of optic nerve damage in glaucoma suspects?

PURPOSE: To evaluate whether treatment of systemic hypertension has an effect on progression of optic nerve parameters in glaucoma suspects using confocal scanning laser ophthalmoscopy. METHODS: Two hundred eyes of 103 glaucoma suspect patients were included in this retrospective cohort study. Thirty-one patients (of whom 59 eyes were included in the study) had systemic hypertension under treatment (based on medical history). The remaining 72 age-matched normotensive controls (of whom 141 eyes were included in the study) were not on blood-pressure-lowering medications. Each patient had a follow-up period of at least 4 years with a minimum of four Heidelberg retinal tomograph tests (one baseline and three follow-up scans). The slopes of progression of optic nerve head parameters with time were studied and compared between these two groups using mixed effects regression models. RESULTS: Patients with systemic hypertension showed a statistically significant increase in cup area (slope 0.2, p = 0.03), cup-to-disk area ratio (slope 0.01, p = 0.007), and decrease in rim area (slope -0.4, p = 0.03), rim-to-disk area ratio (slope -0.01, p = 0.005), and global Retinal Nerve Fiber Layer (RNFL) thickness (p = 0.008) with time. The differences in slopes of progression of many parameters between hypertensives and normotensives were statistically significant. CONCLUSIONS: Systemic hypertension treated with hypotensive medications may be a risk factor for increased progression of optic nerve parameters in glaucoma suspects compared with age-matched normotensive subjects.

Documentation of optic nerve pit with macular schisis-like cavity by spectral domain OCT.

The authors report using spectral domain optical coherence tomography (OCT) to observe a patient with an optic nerve pit and macular schisis-like spaces. An 8-microm axial resolution prototype spectral domain OCT and stereo fundus photography were used to observe the patient. A macular schisis-like cavity was present at baseline and additional cystic changes developed in the nerve fiber layer over a period of 16 months; however, the visual acuity remained stable at 20/20. Spectral domain OCT provides greater detail of the changes in morphology and structure of macular schisis and edema associated with an optic nerve pit.

Documentation by spectral domain OCT of spontaneous closure of idiopathic macular holes.

An observational case series using an 8-microm axial resolution prototype spectral domain optical coherence tomography (OCT) system was performed in two patients with idiopathic macular holes. Spontaneous closure and visual acuity improvement occurred in both patients. Useful information about morphology and vitreoretinal relationship of the holes was provided by spectral domain OCT.

Assessment of ischemia in acute central retinal vein occlusion from inner retinal reflectivity on spectral domain optical coherence tomography.

PURPOSE: To determine the relationship between different spectral domain optical coherence tomography (SD-OCT) signs of retinal ischemia in acute central retinal vein occlusion (CRVO) and whether they predict anterior segment neovascularization (ASNV). DESIGN: Retrospective, observational study. SUBJECTS: Thirty-nine consecutive patients with acute CRVO and 12 months of follow-up. METHODS: We graded baseline SD-OCTs for increased reflectivity of the inner retina, loss of definition of inner retinal layers, presence of a prominent middle-limiting membrane (p-MLM) sign, and presence of paracentral acute middle maculopathy (PAMM). Graders were masked with respect to all clinical information. RESULTS: The intraclass correlation coefficients (ICCs) of grading-regrading by graders 1 and 2 were 0.8104, 95% confidence interval (CI) (0.6686, 0.8956), and 0.7986, 95% CI (0.6475, 0.8892), respectively. The intragrader coefficients of repeatability (COR) for graders 1 and 2 were 0.94 and 0.92, respectively. The ICC of graders 1 compared with 2 was 0.8039, 95% CI (0.6544, 0.8916). The intergrader COR was 0.80. SD-OCT grades of baseline ischemia were not associated with baseline visual acuity (VA), central subfield mean thickness (CSMT), or relative afferent pupillary defect; 12-month VA, CSMT, change in VA, change in CSMT, number of antivascular endothelial growth factor injections or corticosteroid injections, or proportion of eyes developing ASNV. SD-OCT grades of ischemia did not correlate with the proportion of eyes having the p-MLM sign or PAMM. PAMM and p-MLM are milder signs of ischemia than increased reflectivity of the inner retinal layers. Eyes with PAMM can evolve, losing PAMM and gaining the p-MLM sign. CONCLUSION: Grading of ischemia from SD-OCT in acute CRVO was repeatable within graders and reproducible across graders for the graders in this study. SD-OCT signs of ischemia are not correlated with each other and do not reliably predict subsequent ASNV. Close monitoring of eyes with acute CRVO continues to be the safest method to avoid missing ASNV and neovascular glaucoma.