OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FEATURES OF SUBRETINAL FIBROSIS AFTER MYOPIC NEOVASCULARIZATION.

PURPOSE: To describe the optical coherence tomography (OCT) angiography features of subretinal fibrosis in eyes with myopic choroidal neovascularization after natural evolution or secondary to intravitreal anti-vascular endothelial growth factor therapy. METHODS: Retrospective observational case series. All eyes underwent a multimodal imaging examination including fluorescein angiography, spectral domain OCT, OCT angiography, and en face OCT. RESULTS: Twenty-five eyes of 25 patients with mean age of 56.4 ± 14.9 were included in the study. Subretinal fibrosis was diagnosed at mean 30 (range 6-116) months before inclusion. Within the subretinal fibrosis, an abnormal vascular network was observed in 20/25 (80%) eyes, located typically in the outer retina (18/20, 90%) or the choriocapillaris (14/20, 70%) segmentation. The most prevalent patterns were "round tangle" and "tapered tangle." On en face OCT, the subretinal fibrosis was evidenced in 24/25 (96%) eyes, most prevalently in the outer retina (21/25, 84%) and in the choriocapillaris (18/25, 72%), where main feature was white-hyperreflective (20/21, 95%) and dark-hyporeflective (17/18, 94%) appearance, respectively. The presence of subretinal fibrosis on en face OCT was positively correlated with the presence of abnormal vascular network on OCT angiography in 61% of the cases (P = 0.005). CONCLUSION: Subretinal fibrosis secondary to myopic choroidal neovascularization frequently contains blood flow within a persistent abnormal vascular network as assessed by OCT angiography.

The Incidence of Neovascularization in the Fellow Eye of Patients with Unilateral Choroidal Lesion: A Survival Analysis.

PURPOSE: To compare the difference in the rate of survival of unaffected fellow eyes between choroidal neovascularization (CNV) in the first eyes and retinal angiomatous proliferation (RAP) in the first eyes. DESIGN: Cohort retrospective study. PARTICIPANTS: A total of 329 consecutive patients enrolled in our Eye Clinic between February 2006 and November 2014 were involved in the study. Only patients with naïve unilateral forms of neovascularization in 1 eye were included in this study. METHODS: A clinical database containing patients' data and ocular history was evaluated. Only patients with naive lesions in 1 eye and without signs of neovascular AMD in the fellow eye were included in the analysis. The time of absence of neovascularization in the fellow eye was calculated. MAIN OUTCOME MEASURES: Survival of the fellow eye was estimated by Kaplan-Meier analysis, and log-rank test was used to compare CNV and RAP fellow eye survival. RESULTS: A total of 202 eyes affected by CNV and 39 eyes affected by RAP were enrolled in the study. The mean follow-up time was 2.9 years (range, 182-2461 days) for CNV and 2.6 years (range, 519-1504 days) for RAP. Kaplan-Meier analysis showed that the 50% of the fellow eyes with CNV did not develop neovascularization for 5.3 years, whereas the 50% of the fellow eyes with RAP did not develop neovascularization for 3.5 years. Log-rank test showed a highly significant difference between the 2 curves (P < 0.002). CONCLUSIONS: This study showed that the incidence of neovascularization in the unaffected fellow eye increases with time, and when the first eye is affected by RAP, the development of a lesion in the second eye is more premature.

Vitrectomy for optic disc pit maculopathy: a long-term follow-up study.

PURPOSE: To evaluate the clinical outcomes of vitrectomy with induction of posterior vitreous detachment for the treatment of optic disc pit maculopathy. METHODS: We retrospectively evaluated medical records and imaging studies of 11 consecutive patients with optic disc pit maculopathy who underwent vitrectomy at Sacco University Hospital, Milan, Italy, between October 2008 and December 2015. Induction of a posterior vitreous detachment (PVD) was the aim of our surgery. Intravitreal injection of ocriplasmin (Jetrea, Thrombogenics USA, Alcon/Novartis EU) was performed before surgery in three eyes of very young patients. Gas tamponade (sulfur hexafluoride (SF6) 20%) was used only in the first five cases. Main outcome measures were anatomic results as determined by optical coherence tomography and postoperative best-corrected visual acuity (BCVA). RESULTS: Before surgery, a macular detachment was present in 10 eyes and a lamellar hole of the outer retina was detected in 9 eyes. Intraoperatively, two iatrogenic paramacular holes developed in two patients during posterior hyaloid dissection. Time to PVD induction appeared to be greatly reduced in the three patients injected with ocriplasmin before surgery. Patients were followed up for a mean of 38 months (range, 18-84) after surgery. Postoperatively, one patient (9%) developed a retinal detachment that was repaired with one additional vitrectomy. Complete resolution of fluid in and under the fovea was achieved in 8 of the remaining 10 eyes (80%) without additional treatment. Reduction of the inner retinal fluid always preceded the decrease of outer retinal fluid, which in turn anticipated the absorption of macular detachment. The macular detachment resolved in a mean of 14 months after surgery. Postoperative BCVA (mean, 0.63) improved significantly compared with preoperative BCVA (mean, 0.27) (P = 0.005). Nine eyes (82%) had a postoperative BCVA of 0.5 or better. CONCLUSION: Vitrectomy with induction of PVD is a safe and successful therapeutic option for the treatment of optic disc pit maculopathy. The adjunct of ocriplasmin might facilitate the induction of PVD and reduce the risk of iatrogenic retinal holes.

Quantitative fundus autofluorescence in mice: correlation with HPLC quantitation of RPE lipofuscin and measurement of retina outer nuclear layer thickness.

PURPOSE: Our study was conducted to establish procedures and protocols for quantitative autofluorescence (qAF) measurements in mice, and to report changes in qAF, A2E bisretinoid concentration, and outer nuclear layer (ONL) thickness in mice of different genotypes and age. METHODS: Fundus autofluorescence (AF) images (55° lens, 488 nm excitation) were acquired in albino Abca4(-/-), Abca4(+/-), and Abca4(+/+) mice (ages 2-12 months) with a confocal scanning laser ophthalmoscope (cSLO). Gray levels (GLs) in each image were calibrated to an internal fluorescence reference. The bisretinoid A2E was measured by quantitative high performance liquid chromatography (HPLC). Histometric analysis of ONL thicknesses was performed. RESULTS: The Bland-Altman coefficient of repeatability (95% confidence interval) was ±18% for between-session qAF measurements. Mean qAF values increased with age (2-12 months) in all groups of mice. qAF was approximately 2-fold higher in Abca4(-/-) mice than in Abca4(+/+) mice and approximately 20% higher in heterozygous mice. HPLC measurements of the lipofuscin fluorophore A2E also revealed age-associated increases, and the fold difference between Abca4(-/-) and wild-type mice was more pronounced (approximately 3-4-fold) than measurable by qAF. Moreover, A2E levels declined after 8 months of age, a change not observed with qAF. The decline in A2E levels in the Abca4(-/-) mice corresponded to reduced photoreceptor cell viability as reflected in ONL thinning beginning at 8 months of age. CONCLUSIONS: The qAF method enables measurement of in vivo lipofuscin and the detection of genotype and age-associated differences. The use of this approach has the potential to aid in understanding retinal disease processes and will facilitate preclinical studies.

Fundus autofluorescence findings in a mouse model of retinal detachment.

PURPOSE: Fundus autofluorescence (fundus AF) changes were monitored in a mouse model of retinal detachment (RD). METHODS: RD was induced by transscleral injection of hyaluronic acid (Healon) or sterile balanced salt solution (BSS) into the subretinal space of 4-5-day-old albino Abca4 null mutant and Abca4 wild-type mice. Images acquired by confocal scanning laser ophthalmoscopy (Spectralis HRA) were correlated with spectral domain optical coherence tomography (SD-OCT), infrared reflectance (IR), fluorescence spectroscopy, and histologic analysis. Results. In the area of detached retina, multiple hyperreflective spots in IR images corresponded to punctate areas of intense autofluorescence visible in fundus AF mode. The puncta exhibited changes in fluorescence intensity with time. SD-OCT disclosed undulations of the neural retina and hyperreflectivity of the photoreceptor layer that likely corresponded to histologically visible photoreceptor cell rosettes. Fluorescence emission spectra generated using flat-mounted retina, and 488 and 561 nm excitation, were similar to that of RPE lipofuscin. With increased excitation wavelength, the emission maximum shifted towards longer wavelengths, a characteristic typical of fundus autofluorescence. CONCLUSIONS: In detached retinas, hyper-autofluorescent spots appeared to originate from photoreceptor outer segments that were arranged within retinal folds and rosettes. Consistent with this interpretation is the finding that the autofluorescence was spectroscopically similar to the bisretinoids that constitute RPE lipofuscin. Under the conditions of a RD, abnormal autofluorescence may arise from excessive production of bisretinoid by impaired photoreceptor cells.