Avastin as Effective as Eylea for Treating CRVO A clinical trial funded by the National Eye Institute showed monthly injections of Avastin (bevacizumab) were as effective as the drug Eylea (aflibercept) for treatment of central retinal vein occlusion... Patient Recruitment Completed in Abicipar Pegol nAMD Phase III Studies Molecular Partners, a clinical-stage biopharmaceutical company developing a new class of drugs known as DARPin therapies, announced that strategic partner Allergan completed patient recruitment in two global AMD Phase III studies of abicipar pegol... And More...

Six-month VA & Retinal Thickness Outcomes in ME Secondary to CRVO or HRVO: SCORE2 Study Report 4

Researchers wrote that macular edema is the leading cause of decreased visual acuity associated with retinal vein occlusion, so identifying factors associated with better outcomes in RVO eyes treated with anti-vascular endothelial growth factor therapy may provide information useful in counseling patients. As such, they assessed baseline characteristics associated with six-month VA and central subfield thickness outcomes in participants in the Study of Comparative Treatments for Retinal Vein Occlusion 2.

A total of 362 individuals with central RVO or hemi-RVO were enrolled between September 17, 2014, and November 18, 2015, and randomized 1:1 in a masked fashion to receive bevacizumab or aflibercept. At month six, researchers measured the VA outcomes of 348 participants (96 percent) and the spectral-domain optical coherence tomography outcomes of 335 participants (93 percent). The current data analysis was conducted from February 27, 2017, to April 7, 2017.

Eyes were randomly assigned to receive an intravitreal injection of bevacizumab 1.25 mg or aflibercept 2 mg at baseline and every four weeks, with the primary outcome measured at six months. Main outcomes and measures included: change from baseline in VA letter score; VALS gain of 15 or more; change from baseline in CST; CST less than 300 µm; and resolution of ME. Baseline factors associated with six-month outcome at the 0.05 level in univariate regressions were included in multivariate regressions, with outcomes considered to be significant after applying multiplicity control by the Hochberg method.

The mean (SD) age of individuals was 69 (12) years, and 43 percent were women. Younger age (odds ratio, 0.95 per year of age; CI, 0.93 to 0.98; p=0.007) and lower baseline VALS (OR, 0.96 per letter; CI, 0.94 to 0.98; p<0.001) were associated with a six-month VALS gain of 15 or greater. Compared with bevacizumab, aflibercept was associated with a higher odds of ME resolution (OR, 3.59; CI, 2.22 to 5.80; p<0.001) and CST less than 300 µm (OR, 5.30; CI, 2.40 to 11.67; p=0.001), but not with a better VA outcome. Macular edema was less likely to resolve in eyes that received anti-VEGF treatment prior to study participation (OR, 0.33; CI, 0.17 to 0.64; p=0.03).

In eyes treated with bevacizumab or aflibercept, younger age and worse baseline VALS were associated with better six-month VA outcomes. Aflibercept treatment was associated with more favorable SD-OCT outcomes but not VA outcomes. Researchers concluded that these findings might be useful in assessing expected response at month six after monthly injection of anti-VEGF agents for treating ME due to CRVO and HRVO. (Other findings from a different report from the SCORE2 study appear in the first item of “In the News” below.)

Source: Scott IU, VanVeldhuisen PC, Ip MS, et al. Baseline factors associated with 6-month visual acuity and retinal thickness outcomes in patients with macular edema secondary to central retinal vein occlusion or hemiretinal vein occlusion: SCORE2 study report 4. JAMA Ophthalmol 2017; May 9. [Epub ahead of print].

Analysis of a Clinical Trial Comparing Aflibercept, Bevacizumab & Ranibizumab for DR Change

Researchers wrote that anti-vascular endothelial growth factor therapy for diabetic macular edema has been shown to impact diabetic retinopathy improvement and worsening and that it’s unknown whether these effects differ across anti-VEGF agents. As such, they sought to compare changes in DR severity during aflibercept, bevacizumab and ranibizumab treatment for DME. They conducted a secondary analysis of data from a comparative effectiveness trial for center-involved DME in 650 participants receiving aflibercept, bevacizumab or ranibizumab. Retinopathy improvement and worsening were determined during two years of treatment. Participants were randomized between 2012 and 2013, and the trial concluded in September 2015. Interventions included random assignment to aflibercept 2 mg, bevacizumab 1.25 mg and ranibizumab 0.3 mg up to every four weeks through two years following a retreatment protocol. Main outcomes and measures included percentages with retinopathy improvement at one and two years, and cumulative probabilities for retinopathy worsening through two years without adjustment for multiple outcomes.

A total of 650 participants (495 [76.2 percent] with nonproliferative DR and 155 with proliferative DR) were analyzed; 302 (46.5 percent) were women with mean (SD) age of 61 years; 425 (65.4 percent) were white.
• At one year, of 423 NPDR eyes, 44 of 141 (31.2 percent) treated with aflibercept, 29 of 131 (22.1 percent) treated with bevacizumab and 57 of 151 (37.7 percent) treated with ranibizumab had improvement in DR severity (adjusted difference: 11.7 percent: CI, 2.9 percent to 20.6 percent [p=0.004] for aflibercept vs. bevacizumab; 8.9 percent: CI, 1.7 percent to 16.1 percent [p=0.01] for ranibizumab vs. bevacizumab; and 2.9 percent: CI, -5.7 percent to 11.4 percent [p=0.51] for aflibercept vs. ranibizumab).
• At two years, 33 eyes (24.8 percent) in the aflibercept group, 25 eyes (22.1 percent) in the bevacizumab group and 40 eyes (31.0 percent) in the ranibizumab group had DR improvement; no treatment group differences were identified.
• For 93 eyes with PDR at baseline, one-year improvement rates were 75.9 percent for aflibercept, 31.4 percent for bevacizumab and 55.2 percent for ranibizumab (adjusted difference: 50.4 percent: CI, 26.8 percent to 74 percent [p<0.001] for aflibercept vs. bevacizumab; 20.4 percent: CI, -3.1 percent to 44 percent [p=0.09] for ranibizumab vs bevacizumab; and 30 percent: CI, 4.4 percent to 55.6 percent [p=0.02] for aflibercept vs ranibizumab).
• These rates and treatment group differences appeared to be maintained at two years. Despite the reduced numbers of injections in the second year, 66 (59.5 percent) of NPDR and 28 (70 percent) of PDR eyes that manifested improvement at one year maintained improvement at two years.
• Two-year cumulative rates for retinopathy worsening ranged from 7.1 percent to 10.2 percent among anti-VEGF groups for NPDR eyes, and 17.2 percent to 26.4 percent among anti-VEGF groups for PDR eyes. No statistically significant treatment differences were noted.

Researchers concluded that, at one and two years, eyes with NPDR receiving anti-VEGF treatment for DME might experience improvement in DR severity. They found that less improvement was demonstrated with bevacizumab at one year than with aflibercept or ranibizumab. Aflibercept was associated with more improvement at one and two years in the smaller subgroup of participants with PDR at baseline, and all three anti-VEGF treatments were associated with low rates of DR worsening. Researchers suggested that the data provided additional insights to be considered when choosing an anti-VEGF agent to treat DME.

SOURCE: Bressler SB, Liu D, Glassman AR, et al. Change in diabetic retinopathy through 2 years: Secondary analysis of a randomized clinical trial comparing aflibercept, bevacizumab, and ranibizumab. JAMA Ophthalmol 2017; Apr 27. [Epub ahead of print].

Teleophthalmology Image-based Navigated Retinal Laser Therapy for DME

Scientists determined the feasibility and efficacy of a retinal telephotocoagulation treatment plan for diabetic macular edema, as part of a prospective, interventional cohort study at two clinical sites.

Sixteen eyes of 10 subjects with DME underwent navigated focal laser photocoagulation using a novel teleretinal treatment plan. Clinic 1 (King Khaled Eye Specialist Hospital; Riyadh, Saudi Arabia) collected retinal images and fundus fluorescein angiograms. Clinic 2 (Palmetto Retina Center; West Columbia, S.C.) created image-based treatment plans based on which macular laser photocoagulation was performed back at clinic 1.

The primary outcome of the study was the feasibility of image transfer and performing navigated laser photocoagulation for subjects with DME between two distant clinics. Secondary measures were change in best-corrected visual acuity and central retinal thickness by spectral-domain optical coherence tomography three months after treatment.

The teleretinal treatment plan was completed in all 16 eyes. The mean logMAR BCVA at baseline was 0.49 ±0.1, which remained stable (0.45 ±0.1) three months after treatment (p=0.060). The CRT improved from 290.1 μm ±37.6 μm at baseline to 270.8 μm ± 27.7 μm at three months after treatment (p=0.005). All eyes demonstrated improvement in retinal edema after laser photocoagulation, and no eyes demonstrated VA loss three months after treatment.

This study introduced the concept of retinal telephotocoagulation for DME, and demonstrated the feasibility and safety of using telemedicine to perform navigated retinal laser treatments regardless of geographical distance, scientists wrote.

SOURCE: Kozak I, Payne JF, Schatz P, et al. Teleophthalmology image-based navigated retinal laser therapy for diabetic macular edema: A concept of retinal telephotocoagulation. Graefes Arch Clin Exp Ophthalmol 2017; Apr 26. [Epub ahead of print].

Angiopoietin-like Protein 8 & VEGF in PDR

Scientists analyzed the vitreous and serum levels of angiopoietin-like protein 8 and vascular endothelial growth factor in individuals with proliferative diabetic retinopathy. The serum levels of these factors also were analyzed in individuals with diabetes and no diabetic retinopathy, and with non-proliferative diabetic retinopathy to detect the possible correlation between ANGPTL-8 levels and hyperlipidemia.

Scientists obtained vitreous samples from 28 individuals with PDR, and 12 people without diabetes and with idiopathic macular hole. They also obtained serum samples from 26 individuals with NDR and 22 people with NPDR. They determined ANGPTL-8 levels and other factors using an enzyme-linked immunosorbent assay.

ANGPTL-8 and VEGF levels in the vitreous and serum of individuals with PDR were higher than in those with IMH, and were significantly correlated. The vitreous and serum ANGPTL-8 levels were more correlated with triglyceride and low-density lipoprotein cholesterol levels than with high-density lipoprotein cholesterol or total cholesterol levels in those with PDR.

Scientists concluded that vitreous and serum ANGPTL-8 levels were upregulated in individuals with PDR, as they found an association between elevation in ANGPTL-8 levels and angiogenic and hyperlipidemic factors in those with PDR. They wrote that the results suggested that ANGPTL-8 was a potential new diagnostic marker and therapeutic target for PDR treatment.

SOURCE: Lu Q, Lu L, Chen W, et al. Expression of angiopoietin-like protein 8 correlates with VEGF in patients with proliferative diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 2017; Apr 29. [Epub ahead of print].

Sensitivity & Specificity of OCTA for Detecting Choroidal Neovascularization

Investigators determined the sensitivity and specificity of optical coherence tomography angiography in the detection of choroidal neovascularization in age-related macular degeneration, as part of a prospective case series. They studied 72 eyes, including eyes with treatment-naive CNV due to AMD and non-neovascular AMD, and normal controls. Two of the authors have a financial interest in OCTA maker, Optovue.

All eyes underwent OCTA with a spectral-domain OCT. The three-dimensional angiogram was segmented into separate en face views including the inner retinal angiogram, outer retinal angiogram and choriocapillaris angiogram. Detection of abnormal flow in the outer retina served as candidate CNV with OCTA. Masked graders reviewed structural OCT alone, en face OCTA alone and en face OCTA combined with cross-sectional OCTA, for the presence of CNV.

The main outcome measure included the sensitivity and specificity of CNV detection compared with fluorescein angiography.

Of 32 eyes with CNV, both graders identified 26 true positives with en face OCTA alone, resulting in a sensitivity of 81.3 percent. Four of the six false negatives had large subretinal hemorrhages, and sensitivity improved to 94 percent for graders if eyes with subretinal hemorrhages were excluded. The addition of cross-sectional OCTA along with en face OCTA improved sensitivity to 100 percent for both graders. Structural OCT alone also had a sensitivity of 100 percent. The specificity of en face OCTA alone was 92.5 percent for grader A and 97.5 percent for grader B. The specificity of structural OCT alone was 97.5 percent for grader A and 85 percent for grader B. Cross-sectional OCTA combined with en face OCTA had a specificity of 97.5 percent for grader A and 100 percent for grader B.

Investigators concluded that:
• sensitivity and specificity for CNV detection with en face OCTA combined with cross-sectional OCTA approached that of the gold standard method of fluorescein angiography with OCT and was better than en face OCTA alone;
• structural OCT alone had excellent sensitivity for CNV detection; and
• false positives from structural OCT could be mitigated with the addition of flow information with OCTA.

SOURCE: Faridi A, Jia Y, Gao SS, et al. Sensitivity and specificity of OCT angiography to detect choroidal neovascularization. Ophthalmology Retina 2017; April 19. [Epub ahead of print].

HDL Cholesterol-associated Mechanisms in AMD Etiology

Investigators conducted a systematic investigation into associations between genetic predictors of lipid fractions and age-related macular degeneration risk, as part of a two-sample Mendelian randomization investigation using published data.

A total of 33,526 individuals (16,144 cases, 17,832 controls) predominantly of European ancestry from the International Age-related Macular Degeneration Genomics Consortium were included.

Investigators considered 185 variants previously demonstrated to be associated with at least one low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides, at a genome-wide level of significance and tested their associations with AMD. They focused on variants in gene regions that were proxies for specific pharmacologic agents for lipid therapy and then conducted a two-sample Mendelian randomization investigation to assess the causal roles of LDL cholesterol, HDL cholesterol and triglycerides on AMD risk. Investigators also conducted parallel investigations for coronary artery disease (viewed as a positive control) and Alzheimer's disease (a negative control) for comparison. The main outcome measure was the diagnosis of AMD.

Investigators found evidence that HDL cholesterol was a causal risk factor for AMD, with an odds ratio estimate of 1.22 (CI, 1.03 to 1.44) per one standard deviation increase in HDL cholesterol. However, they found no causal effect of LDL cholesterol or triglycerides. They determined that variants in the CETP gene region associated with increased circulating HDL cholesterol also were linked to increased AMD risk, although variants in the LIPC gene region that increased circulating HDL cholesterol had the opposite association with AMD risk. Parallel analyses suggested that lipids play a greater role in AMD compared with Alzheimer's disease, but a lesser role than in coronary artery disease.

Investigators determined that some genetic evidence suggested that HDL cholesterol was a causal risk factor for AMD risk and that increasing HDL cholesterol (particularly via CETP inhibition) would increase AMD risk.

SOURCE: Burgess S, Davey Smith G, et al. Mendelian randomization implicates high-density lipoprotein cholesterol-associated mechanisms in etiology of age-related macular degeneration. Ophthalmology 2017; Apr 26. [Epub ahead of print].

Adalimumab for Noninfectious Intermediate Uveitis, Posterior Uveitis and Panuveitis in the VISUAL-1 and -2 Trials

To assess the effect of adalimumab on the visual functioning and quality of life in individuals with corticosteroid-dependent noninfectious intermediate uveitis, posterior uveitis and panuveitis, researchers conducted a post hoc analysis of AbbVie’s clinical trials of adults with active (VISUAL-1) and inactive (VISUAL-2) noninfectious intermediate uveitis, posterior uveitis and panuveitis in the United States, Canada, Europe, Israel, Australia, Latin America and Japan.

They studied 217 individuals (110 adalimumab, 107 placebo) in VISUAL-1, and 226 cases (115 adalimumab, 111 placebo) in VISUAL-2 using intent-to-treat analyses. The clinical trials were conducted between August 10, 2010, and May 14, 2015.

In VISUAL-1 and VISUAL-2, individuals were randomized to receive adalimumab 80 mg subcutaneous loading doses followed by 40 mg every other week or placebo for 80 weeks. All individuals underwent prednisone tapering, with individuals in VISUAL-1 receiving an initial prednisone burst.

The 25-item National Eye Institute Vision Function Questionnaire composite score assessed the impact of visual impairment from the individual’s perspective; scores range from 0 to 100, with higher scores indicating better vision-related quality of life.The change in NEI VFQ-25 from best state achieved prior to week six (VISUAL-1) and from baseline state (VISUAL-2) to the final or early termination visit was determined in each group and statistically compared using analysis of variance. Researchers analyzed the temporal effects of adalimumab and placebo on NEI VFQ-25 using a longitudinal model.

Of 217 individuals in VISUAL-1, 124 (57.1 percent) were women; the mean (SD) age was 42.7 (14.9) years. Of the 226 individuals in VISUAL-2, 138 (61.1 percent) were women; the mean (SD) age was 42.5 (13.4). In VISUAL-1, the change from final score to best score in NEI VFQ-25 was -1.30 for adalimumab and -5.50 for placebo—a difference of 4.20 (CI, 1.04 to 7.36; p=0.01). In VISUAL-2, the change from baseline NEI VFQ-25 was 3.36 for adalimumab and 1.24 for placebo—a difference of 2.12 (CI, -0.81 to 5.04; p=0.16). In both trials, longitudinal models showed a significant difference in NEI VFQ-25 between adalimumab and placebo of: 3.07 (CI, 2.09 to 4.06; p<0.001) in the VISUAL-1 trial (74.15 vs. 71.08); and 4.66 (CI, 0.05 to 9.26; p=0.048) in the VISUAL-2 trial (82.39 vs. 77.73).

Researchers found that adalimumab was associated with statistically significant and clinically meaningful improvements in individual-reported visual functioning for those with noninfectious intermediate uveitis, posterior uveitis and panuveitis.

SOURCE: Sheppard J, Joshi A, Betts KA, et al. Effect of adalimumab on visual functioning in patients with noninfectious intermediate uveitis, posterior uveitis, and panuveitis in the VISUAL-1 and VISUAL-2 Trials. JAMA Ophthalmol 2017; Apr 20. Epub ahead of print.

Risk of Ocular Hypertension in Adults with Noninfectious Uveitis

Researchers sought to describe risk factors for ocular hypertension in adults with noninfectious uveitis, as part of a retrospective, multicenter cohort study. Individuals ages ≥18 years with noninfectious uveitis seen between 1979 and 2007 at five tertiary uveitis clinics were included.

Demographic, ocular and treatment data were extracted from the medical records of uveitis cases. Main outcome measures included prevalent and incident OHT with intraocular pressures of ≥21 mmHg, ≥30 mmHg and an increase of ≥10 mmHg from documented IOP recordings (or OHT treatment).

Among 5,270 uveitic eyes of 3,308 individuals followed for OHT, the mean annual incidence rates were: for OHT ≥21 mmHg, 14.4 percent (CI, 13.4 to 15.5); and for OHT ≥30 mmHg, 5.1 percent (CI, 4.7 to 5.6) per year. Statistically significant risk factors for incident OHT ≥30 mmHg included:
• systemic hypertension (adjusted hazard ratio: 1.29);
• worse presenting visual acuity (≤20/200 vs. ≥20/40, aHR, 1.47);
• pars plana vitrectomy (aHR, 1.87);
• history of OHT in the other eye: IOP ≥21 mmHg (aHR, 2.68), ≥30 mmHg (aHR, 4.86) and prior/current use of IOP-lowering drops or surgery in the other eye (aHR, 4.17);
• anterior chamber cells: 1+ (aHR, 1.43) and ≥2+ (aHR, 1.59) vs. none;
• epiretinal membrane (aHR, 1.25);
• peripheral anterior synechiae (aHR, 1.81);
• current use of prednisone >7.5 mg/day (aHR, 1.86);
• periocular corticosteroids in the last three months (aHR, 2.23);
• current topical corticosteroid use [≥8 times a day vs. none] (aHR, 2.58); and
• prior use of fluocinolone acetonide implants (aHR, 9.75). Bilateral uveitis (aHR, 0.69) and previous hypotony (aHR, 0.43) were associated with statistically significantly lower risk of OHT.

Based on the prevalence of ocular hypertension in eyes treated for uveitis in this study, researchers recommended surveillance for OHT at all visits for all cases. They added that individuals with one or more of the risk factors identified were at particular risk, and such cases must be carefully managed. Furthermore, researchers wrote, modifiable risk factors such as the use of corticosteroids suggested opportunities to reduce OHT risk within the overriding need to control the primary ocular inflammatory disease.

SOURCE: Daniel E, Pistilli M, Kothari S, et al. Risk of ocular hypertension in adults with noninfectious uveitis. Ophthalmology 2017; Apr 19. [Epub ahead of print].

Long-term Follow-up of Fellow Eyes With Lamellar Macular Hole

Investigators evaluated macular changes in the fellow eyes of individuals diagnosed with lamellar macular hole using spectral-domain optical coherence tomography and blue fundus autofluorescence.

They retrospectively evaluated the fellow eyes of individuals diagnosed with a LMH on OCT, recorded best-corrected visual acuity and central foveal thickness, and examined corresponding B-FAF images, vitreo-macular relations and type of epiretinal membranes.

Thirty-five individuals were included. At baseline, six fellow eyes (17 percent) showed a normal foveal profile, 26 (74 percent) had a tractional ERM and three cases (9 percent) revealed a bilateral LMH, one of them with a lamellar hole-associated epiretinal proliferation. A posterior vitreous detachment was present in 29 individuals (83 percent), four (11 percent) had only a vitreo-papillary adhesion, and two (6 percent) had both vitreo-macular adhesion and VPA. After a mean follow-up of 4.6 ±1.9 years, one eye (3 percent) developed a vitreous detachment from the macula with persistent VPA, and one developed a PVD from a VPA with subsequent ERM formation.

BCVA and mean CFT remained stable in 35 eyes (100 percent). Likewise, no B-FAF signal variations were detected. One individual developed a LMH during the third year of follow-up.

Investigators found that the presence of a LMH in one eye didn’t significantly increase the risk of developing the same condition in the fellow eye after four years. Bilateral presence was uncommon, and an ERM was often detected in the fellow eye. LHEPs were not observed in fellow eyes with foveal integrity, and all LHEPs observed (in main and fellow eyes) were always associated with LMHs. These findings supported the hypothesis that LHEP is a consequence of, and not a causative factor for, LMHs. Investigators wrote that the occurrence of a LMH in one fellow eye after three-year follow-up might suggest that a higher incidence of bilateral disease could develop in a longer time span.

SOURCE: Nava U, Cereda MG, Bottoni F. Long-term follow-up of fellow eye in patients with lamellar macular hole. Graefes Arch Clin Exp Ophthalmol 2017; Apr 13. [Epub ahead of print].

Correlation of Radial Peripapillary Capillary Density Network With RNFL Thickness

Researchers analyzed the expansion of the radial peripapillary capillary network with optical coherence tomography angiography in normal human eyes, and correlated RPC density with retinal nerve fiber layer thickness at various distances from the optic nerve head edge.

Fifty eyes of 50 healthy subjects underwent imaging with RTVue XR-100 Avanti OCT. Researchers combined OCTA scans of Angio disc (6 mm × 6 mm) and Angio retina (8 mm × 8 mm) to create a wide-field montage image of the RPC network. They calculated RPC density and RNFLT at different circle diameters around the ONH, and measured their correlation.

In the arcuate region, RPC was detected as far as 8.5 mm from the ONH edge, but not around the perifoveal area within 0.025 mm² ±0.01 mm². The mean RPC density (0.1556 ±0.015) and RNFLT (245.96 ±5.79) were highest at 1.5 mm from the ONH margin, and a trend was detected in its decline in a distance-dependent manner, with the least density at 8.5 mm (all p<0.0001). Highest RPC density was noted in the arcuate fiber region at all the distances. Overall mean RPC density correlated significantly (p<0.0001) with the overall mean RNFLT.

Researchers suggested that wide-field montage OCTA angiograms could visualize expansion of the RPC network, which could be useful in obtaining information about various retinal disorders. The results supported the hypothesis that the RPC network could be responsible for RNFL nourishment, researchers added.

SOURCE: Mansoori T, Sivaswamy J, Gamalapati JS, et al. Topography and correlation of radial peripapillary capillary density network with retinal nerve fibre layer thickness. Int Ophthalmol 2017; Apr 26. [Epub ahead of print].

Evolution of Outer Retinal Tubulation, a Neurodegeneration and Gliosis in Macular Diseases

To document outer retinal tubulation formation in advanced retinal disorders, investigators conducted a retrospective, observational study. They included consecutive cases with retinal diseases showing outer retinal disruption and atrophy of the retinal pigment epithelium associated with ORT on spectral-domain optical coherence tomography.

Investigators compared cross-sectional SD-OCT scans showing ORT at the last available visit with eye-tracked baseline scans. Only individuals showing formation of ORT over time with absence of ORT at baseline were analyzed.

Main outcome measures included steps in ORT formation based on shapes of the external limiting membrane descent (flat, curved, reflected and scrolled) at the border of the outer retinal region; and RPE atrophy, ORT characteristics (open, closed) and time between steps through a long-term follow-up.

From 170 eyes of 86 individuals with ORT, 38 eyes of 30 people (11 men, 19 women) with a mean age of 78.87 years (range, 56 to 96 years) met inclusion criteria. Of these 38 eyes, 23 (60 percent) had geographic atrophy secondary to age-related macular degeneration and two eyes (5 percent) had geographic atrophy secondary to pattern dystrophy. Twelve eyes (32 percent) had neovascular AMD and one eye (3 percent) had neovascularization secondary to pseudoxanthoma elasticum, all showing similar ORT formative steps. Investigators analyzed 73 different retinal areas (1,434 cross-sectional images) over a mean follow-up period of 69.5 months (range, 21 to 93 months). At 73 borders, grading of eye-tracked SD-OCT line scans showed a flat ELM descent at least once at 34 borders (47 percent), a curved ELM at 47 borders (64 percent), a reflected ELM at 37 borders (51 percent) and a scrolled ELM at 24 borders (33 percent). Of 81 ORTs, 73 (90 percent) were closed and eight (10 percent) were open. The mean time for ORT formation was 14.9 months (range, 1.4 to 71.3 months).

Investigators proposed progressive steps in the development of ORT and analyzed the time of progression between these steps. They found that analyzing the borders of atrophy to determine ORT origin provided new insights into the pathophysiology of advanced retinal disease, highlighting a role for Müller cells that might inform future therapeutic strategies.

SOURCE: Dolz-Marco R, Litts KM, Tan ACS, et al. The evolution of outer retinal tubulation, a neurodegeneration and gliosis prominent in macular diseases. Ophthalmology 2017; Apr 26. [Epub ahead of print].