Outer Retinal Layer Thickening Predicts the Onset of Exudative Neovascular Age-Related Macular Degeneration.

PURPOSE: To assess changes in outer retinal layer (ORL) thickness before the development of exudative macular neovascularization (MNV) in eyes with age-related macular degeneration. DESIGN: Retrospective observational case series. METHODS: Eyes with age-related macular degeneration that eventually developed exudative MNV followed with sequential optical coherence tomography for ≥2 years before the exudation occurred were enrolled. The ORL thickness was automatically calculated by the optical coherence tomography software for each sector of the early treatment diabetic retinopathy study map at each follow-up visit. The ORL thickness change from baseline to the day when the exudative MNV developed was compared between sectors that eventually developed exudative MNV and those that did not. RESULTS: Forty-seven eyes (47 patients) were included. At baseline (24 ± 3 months before exudative MNV), mean (standard deviation) ORL thickness of sectors that eventually developed exudative MNV was similar to that of sectors that did not (85.2 [8.2] µm vs 86.8 [5.7] µm, P = .08). ORL thickness significantly increased in sectors that developed exudative MNV compared with those that did not (+5.8 [10.4] µm vs -2.8 [3.6] µm, P < .01). The regression model based on these data predicted an increase in ORL thickness from baseline of +4.2% 55 days and +11.1% 30 days before exudative MNV was detected. The ORL thickness of areas that did not develop exudative MNV did not change. CONCLUSION: Thickening of the ORL begins in the area where exudative MNV will develop long before the exudation, accelerating significantly in the last 2 months. The occurrence of exudative MNV could be predicted by 2 months using this simple analysis.

OPTICAL COHERENCE TOMOGRAPHY 2: Diagnostic Tool to Study Peripheral Vitreoretinal Pathologies.

PURPOSE: To investigate the utility of new wide-field optical coherence tomography (OCT) device in the evaluation of mid and far retinal periphery and to show its feasibility and advantages in clinical practice. METHODS: Consecutive patients underwent a complete ophthalmologic examination including standard OCT and new prototype OCT2 derived from Heidelberg Spectralis. RESULTS: Thirty-one eyes of 31 patients were studied with a total of 44 lesions, including 18 retinal detachments, 15 retinal holes and tears, 9 retinoschisis, and 2 retinal tufts. Fourteen (32%) lesions were found in mid and 30 (68%) in far periphery with 9 (20%) lesions in the superior region, 10 (23%) in the superior temporal, 8 (18%) in the temporal, 4 (9%) in the inferior temporal, 7 (16%) in the inferior, 4 (9%) in the nasal, and 2 (5%) in the superior nasal. Among the lesions evaluated by OCT2, 10 (71%) in mid periphery and 11 (37%) in far periphery could be imaged by standard OCT. CONCLUSION: The introduction of OCT2 into clinical practice may provide significant benefits for imaging peripheral retinal disorders. The application of OCT2 technology with 55° lens and scan length and angle modulation could improve our understanding of peripheral vitreoretinal disorders and facilitate their management.

DEVELOPMENT AND PROGRESSION OF A LAMELLAR MACULAR HOLE WITH LAMELLAR HOLE-ASSOCIATED EPIRETINAL PROLIFERATION.

PURPOSE: To describe evolution and progression of a lamellar macular hole (LMH) with "lamellar hole-associated epiretinal proliferation (LHEP)" using spectral-domain optical coherence tomography and fundus autofluorescence. METHODS: Observational case report. RESULTS: We report on a 63-year-old male patient demonstrating a complete history of LMH development with LHEP occurring during a follow-up period of 8 years. Presenting with a normal foveal contour and attached posterior vitreous at first visit, an LMH developed shortly after incomplete posterior vitreous detachment with vitreopapillary adhesion. On spectral-domain optical coherence tomography images, progression of the LMH including enlargement of the intraretinal cavitation and decrease in the retinal thickness were documented. An increase of LHEP was first documented 6 months after LMH evolution. One month after cataract surgery and 6 years after the first visit, a full-thickness macular hole developed that closed spontaneously after 4 weeks. Localization of LHEP had moved into the foveal defect toward the outer retinal layers. Thereafter, the LMH was stable, and the patient presented with a visual acuity of 20/25. CONCLUSION: Proper follow-up time is important for studying eyes with an LMH. Epimacular cell proliferation shows progression over time that appears to be associated with morphologic changes of the LMH including shape of the lamellar defect, amount of LHEP, and contractive properties of epiretinal tissue. The presence of LHEP was documented shortly after posterior vitreous detachment.

SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN CHOROIDAL MELANOMA: An Analysis of 22 Consecutive Cases.

PURPOSE: To describe the imaging features of choroidal melanoma using swept-source optical coherence tomography angiography (SS-OCT-A) and to evaluate its ability to display tumor intrinsic vasculature. METHODS: Consecutive patients diagnosed with choroidal melanoma underwent a complete ophthalmic evaluation, including best-corrected visual acuity, color fundus photography, B-scan ultrasound, fluorescein angiography, indocyanine green angiography, and SS-OCT-A (PLEX Elite 9000; Carl Zeiss Meditec, Inc, Dublin, CA). RESULTS: Twenty-two eyes of 22 consecutive patients were included in the study; 11 cases (50%) were treatment naive. Three lesions (14%) were located at the macula, 14 (63%) between the macula and equator, and 5 (23%) between the equator and the ora serrata. The mean tumor base and thickness were, respectively, 10.3 mm (range 5-15 mm) and 4.3 mm (range 1.5-8.9 mm). Seventeen lesions (77%) were dome shaped, whereas 5 (23%) had a mushroom configuration. Thirteen lesions (59%) were pigmented, 5 (23%) partially pigmented, and 4 (18%) amelanotic. An exudative retinal detachment was documented in 13 eyes (59%). Fluorescein angiography and indocyanine green angiography were performed in 20 patients and disclosed intrinsic microvasculature of the tumor, respectively, in 4 (20%) and 20 (100%) cases. Swept-source optical coherence tomography angiography was performed in 22 eyes and detected microvasculature of choroidal melanoma in all cases. Specifically, intrinsic vasculature could be recognized in 14 eyes (64%) using the automated choroid segmentation, 16 eyes (73%) using the automated whole eye segmentation, and in 22 eyes (100%) with fine manual adjustments of segmentation lines. CONCLUSION: Swept-source optical coherence tomography angiography represents a valid imaging technique to evaluate patients affected by choroidal melanomas. In our series, SS-OCT-A disclosed the intrinsic microvasculature of the tumor in all cases despite their size, location, and history of previous treatments.

OCRIPLASMIN FOR VITREOMACULAR TRACTION: LOOKING OUTSIDE THE MACULA: A Wide-Field Optical Coherence Tomography Study.

PURPOSE: To evaluate baseline features and morphologic changes of vitreoretinal adhesion and outer retinal layers outside the macula after intravitreal ocriplasmin injection. To study the relation between vitreous detachment and attenuation of retinal outer segments signal. METHODS: Retrospective cases series of 15 eyes. Each eye was scanned with the 55° wide-field optical coherence tomography lens in 6 different locations, three horizontal B-scan (central, temporal, and nasal) and three vertical B-scan (central, superior, and inferior) at baseline, 1 week, 1 month, 3 months, and 6 months after injection. RESULTS: After ocriplasmin injection, vitreomacular traction (VMT) resolved in 12 patients (80%), 3 of them presenting a complete posterior vitreous detachment. Eight patients (53%) showed a panretinal attenuation of photoreceptors outer segment signal, 7 with VMT resolution and 1 with non-posterior vitreous detachment and no VMT resolution. In three patients after VMT resolution the attenuation involved also areas with no posterior vitreous detachment. The attenuation resolved during follow-up in 7/8 eyes (87.5%). CONCLUSION: Intravitreal ocriplasmin injection induced resolution of VMT in most cases and more rarely a release of vitreopapillary adhesion and a complete posterior vitreous detachment. An acute panretinopathy was visible in more than half of the patients and was not related to vitreous detachment.

Progression of lamellar hole-associated epiretinal proliferation and retinal changes during long-term follow-up.

PURPOSE: To report on progression of lamellar hole-associated epiretinal proliferation (LHEP) in eyes with lamellar macular holes (LMH) using spectral-domain optical coherence tomography (SD-OCT), and to correlate with intraretinal changes and visual function. METHODS: From a retrospectively reviewed series of 167 eyes with non-full-thickness macular holes, we exclusively included a subgroup of 34 eyes with LMH and LHEP by SD-OCT evaluation. In these eyes, area of LHEP, intraretinal changes of defect diameter, central retinal thickness, defects of the ellipsoid zone and occurrence of a contractive epiretinal membrane were analysed. Additionally, clinical data were documented. RESULTS: Area of LHEP significantly increased during a mean follow-up period of 40.5 months (median 52 months). Analysing intraretinal changes, a significant enlargement of minimum and maximum horizontal lamellar hole diameter was found that correlated with the area of LHEP. Defects of the ellipsoid zone were seen in 65% of the eyes at baseline and in 85% at the end of follow-up. Increase of maximum horizontal hole diameter and ellipsoid zone defects correlated with a decline of visual acuity. Fifty per cent of patients with LMH and LHEP also demonstrated extrafoveal typical contractive epiretinal membranes with retinal folds. CONCLUSIONS: Long-term follow-up revealed an increase of the area of LHEP in eyes with LMH that correlated with the enlargement of lamellar hole diameter and ellipsoid zone defects. Our data delineate the progression of intraretinal changes in association with a decline of visual function in this subgroup of LMH eyes.

Choroidal characteristics of acute and chronic central serous chorioretinopathy using enhanced depth imaging optical coherence tomography.

PURPOSE: Central serous chorioretinopathy (CSC) is an idiopathic disorder characterized by serous detachments of the neurosensory retina and/or the retinal pigment epithelium affecting the macular area in the majority of cases. The objective of this study was to describe choroidal findings in patients with acute and chronic CSC based on enhanced depth imaging optical coherence tomography analysis. METHODS: This is a cross-sectional, noninterventional study performed at Luigi Sacco University Hospital of Milan. Inclusion criteria were the presence of diagnosed (acute or chronic) CSC and being 18 years or older. Patients were evaluated with Spectralis spectral-domain optical coherence tomography enhanced depth imaging by 2 operators. The main features analyzed were intrachoroidal hyperreflective spots and hyperreflective choroidal vessel walls, as actual measurements of wall thickness could not be performed. RESULTS: Patients with chronic CSC had hyperreflective spots in 83.3% of the cases and hyperreflective choroidal vessel walls in 75%, whereas patients with acute course had the same alterations in 33% and 6.7% of cases, respectively. CONCLUSIONS: These findings, if proven, may be indicative of chronic forms, thus guiding more accurate treatments and guiding clinicians through more accurate prognosis.

Identifying Predictors of Anti-VEGF Treatment Response in Patients with Neovascular Age-Related Macular Degeneration through Discriminant and Principal Component Analysis.

OBJECTIVE: AURA was an observational study that monitored visual acuity outcomes following ranibizumab use in neovascular age-related macular degeneration patients over 2 years. The aim of this analysis was to identify factors that were predictive of visual acuity outcomes in AURA. METHODS: The correlation between the baseline characteristics, the use of resources and the visual acuity outcomes in AURA was explored using principal component analysis (PCA) and partial least-squares-discriminant analysis (PLS-DA). The response variables analysed were mean change in visual acuity over 2 years (analysed via PCA) and no decline in visual acuity at 2 years compared with baseline (analysed via PLS-DA). RESULTS: The AURA dataset comprised 2,227 patients and 132 variables. Using PCA and PLS-DA, we found that the number of ranibizumab injections, clinic and monitoring visits, number of optical coherence tomography scans and ophthalmoscopies correlated with a change in visual acuity at Years 1 and 2, and are therefore key drivers of treatment success. CONCLUSION: This is a novel approach to graphically explore relationships between multiple correlated covariates and outcomes in real-life ophthalmology studies. It identified a number of variables that are positively linked with treatment outcomes.

INTRAVITREAL VERSUS SUBRETINAL ADMINISTRATION OF RECOMBINANT TISSUE PLASMINOGEN ACTIVATOR COMBINED WITH GAS FOR ACUTE SUBMACULAR HEMORRHAGES DUE TO AGE-RELATED MACULAR DEGENERATION: An Exploratory Prospective Study.

PURPOSE: Current management of submacular hemorrhage (SMH) favors vitrectomy and gas with subretinal administration of recombinant tissue plasminogen activator (rtPA) over mere intravitreal rtPA injections and gas. In this study, we aimed to compare the effectiveness of both treatment modalities to displace submacular blood. METHODS: Twenty-four patients with SMH secondary to age-related macular degeneration were included. The SMH had to exist ≤14 days at time of surgery and SMH thickness had to be between 250 µm and 1,250 µm. Patients were randomized to either intravitreal injections of rtPA, perfluoropropane (C3F8) gas, and bevacizumab (n = 12) or vitrectomy with subretinal rtPA administration, intravitreal C3F8 gas, and bevacizumab (n = 12). The SMH volume change was measured on spectral domain optical coherence tomography postoperatively within a 2.5-mm cylinder centered at the fovea. RESULTS: Median relative volume reduction of subretinal blood at 6 weeks postoperatively was 97% (95% confidence interval: 91-99%) in the intravitreal rtPA group and 100% (95-100%) in the subretinal rtPA group and did not differ significantly between groups (P = 0.56). CONCLUSION: Both treatment modalities effectively displaced SMH in this exploratory clinical trial. To more definitely study the noninferiority of intravitreal rtPA with gas to subretinal rtPA, vitrectomy with gas, a larger clinical trial would be necessary.

Prospective, Randomized Intervention Study Comparing Retinal Pigment Epithelium-Choroid Graft Surgery and Anti-VEGF Therapy in Patients with Exudative Age-Related Macular Degeneration.

PURPOSE: To investigate whether patients with exudative age-related macular degeneration and a submacular hemorrhage, retinal pigment epithelium (RPE) tear or nonresponders to anti-vascular endothelial growth factor (VEGF) benefit more from a free RPE-choroid graft transplantation surgery than from (continuation of) anti-VEGF treatment. PROCEDURES: A total of 20 patients were included in this prospective, international, multicenter, randomized intervention study. RESULTS: The change in the mean number of Early Treatment of Diabetic Retinopathy Study (ETDRS) letters in the graft group 1 year postoperatively was -15 (range -54 to +26), whilst 2 patients experienced a gain of >10 letters. The median preoperative visual acuity (VA) was 0.75 logMAR (range 0.46-2.8), and the mean postoperative VA was 1.48 logMAR (range 0.14-2.8). The change in the mean number of ETDRS letters in the anti-VEGF group was -8 (range -26 to +6); no patients experienced a >10 letter gain. The median preoperative VA was 1.36 logMAR (range 0.58-1.6), and the median postoperative VA was 1.42 logMAR (range 0.44-1.66). CONCLUSIONS: The included patient group is far too small to draw conclusions. However, both gain and loss of VA may be experienced by patients undergoing either treatment method; more gain might be possible for patients with a graft in the absence of complications.

Pearls and pitfalls in diagnosis and management of coats disease.

PURPOSE: To review current literature on Coats disease and provide a structured framework for differentiating challenging clinical features in Coats disease patients. METHODS: We critically reappraise historical and current literature and present clinical methods for developing a thorough differential diagnosis and management strategy for Coats disease. RESULTS: Coats disease is a sporadic, usually unilateral condition typically occurring in young males. When untreated, this disorder can lead to total exudative retinal detachment and secondary glaucoma. CONCLUSIONS: Anti-VEGF agents are currently a treatment option in combination with ablative therapy of telangiectatic vessels. Anti-VEGF agents appear particularly useful for patients with extensive areas of exudative retinal detachment, and are an effective treatment option for total retinal detachment.

Direct Blood Flow Measurements in a Free RPE-Choroid Graft with Phase-Resolved Doppler OCT.

PURPOSE: We directly demonstrated the revascularization in a free retinal pigment epithelium (RPE)-choroid graft with direct blood flow detection by experimental phase-resolved Doppler optical coherence tomography (PRD-OCT). METHODS: Seven patients with age-related macular degeneration underwent an RPE-choroid graft translocation in a prospective institutional cohort study. Spectral domain optical coherence tomography (SD-OCT) was used to measure the revascularization stage. With PRD-OCT the presence of flow was imaged postoperatively. RESULTS: The PRD-OCT confirmed flow in three patients when SD-OCT indicated the afferent vessel ingrowth stage, and in all seven patients when the SD-OCT indicated the efferent vessel ingrowth stage. CONCLUSIONS: The PRD-OCT study was able to detect the presence of blood flow in a free RPE-choroid graft. The PRD-OCT findings directly confirmed the revascularization that was otherwise based on the more circumstantial evidence provided by SD-OCT images and angiography. TRANSLATIONAL RELEVANCE: The use of both techniques to monitor the revascularization process in a free graft in patients are an interesting example of replacing more invasive by noninvasive techniques. There is potential future use of PRD-OCT for the visualization of vascularization patterns in other pathologies.

Multi-country real-life experience of anti-vascular endothelial growth factor therapy for wet age-related macular degeneration.

BACKGROUND/AIMS: Real-life anti-vascular endothelial growth factor (VEGF) therapy use in patients with wet age-related macular degeneration (wAMD) was assessed in a retrospective, observational study in Canada, France, Germany, Ireland, Italy, the Netherlands, UK and Venezuela. METHODS: Medical records of patients with wAMD, who started ranibizumab treatment between 1 January 2009 and 31 August 2009, were evaluated. Data were collected until the end of treatment and/or monitoring or until 31 August 2011. RESULTS: 2227 patients who received ≥1 anti-VEGF injection with a baseline visual acuity assessment and ≥1 postbaseline visual acuity assessment for the treated eye were evaluated. Visual acuity improved until about day 120; thereafter, visual acuity gains were not maintained. Mean change in visual acuity score from baseline to years 1 and 2 was +2.4 and +0.6 letters, respectively. Patients received a mean of 5.0 and 2.2 injections in the first and second year, respectively. There were substantial differences in visual outcomes and injection frequency between countries. More frequent visits and injections were associated with greater improvements in visual acuity. CONCLUSIONS: In clinical practice, fewer injections are administered than in clinical trials. Anti-VEGF treatment resulted in an initial improvement in visual acuity; however, this was not maintained over time. TRIAL REGISTRATION NUMBER: NCT01447043.

Recombinant tissue plasminogen activator, vitrectomy, and gas for recent submacular hemorrhage displacement due to retinal macroaneurysm.

BACKGROUND: The visual prognosis of submacular hemorrhages caused by a retinal arterial macroaneurysm (RAM) is poor if left untreated. The use of recombinant tissue plasminogen activator (rtPA) has frequently been reported to displace submacular hemorrhages from the foveal area in patients with age-related macular degeneration. This study aims to investigate the results of displacement of recent-onset submacular hemorrhages due to RAM. METHODS: Institutional retrospective interventional case series of 12 patients with macular hemorrhage due to RAM, who underwent pars plana vitrectomy (PPV); followed in 11 by submacular injection of rtPA and gas tamponade. The main outcome measures were displacement of the hemorrhage, complication rate, and visual acuity at 1 month after surgery and at the last follow-up visit. RESULTS: One month after surgery, the hemorrhage had been successfully displaced in ten out of 11 patients. In these ten patients, visual acuity (VA) increased by a mean of 1.2 logMAR at 1 month after surgery. At the last follow-up visit, the mean increase was 1.5 logMAR. Complications consisted of a vitreous hemorrhage and hyphema, retinal detachment, a new submacular hemorrhage, and vitreous hemorrhage after argon laser retinal photocoagulation of the RAM. CONCLUSIONS: PPV with submacular rtPA and gas injection may successfully displace a recently developed submacular hemorrhage in patients with RAM, with a marked improvement in VA that is likely to be greater than if left untreated.

Lamellar macular hole: a clinicopathologic correlation of surgically excised epiretinal membranes.

PURPOSE: To correlate clinical and optical coherence tomographic (OCT) features with morphologic and immunohistochemical findings of epiretinal membranes (ERMs) in lamellar macular holes (LMHs). METHODS: Nineteen specimens were removed from 19 eyes during vitrectomy for lamellar macular hole with ERM and internal limiting membrane peeling, and were processed for transmission electron microscopy and immunohistochemistry by cross-sectional and flat-mount preparation techniques. By using OCT criteria and intraoperative observations, ERM specimens were divided into two groups: 13 "dense" and 6 "tractional" membranes. Patients' records were reviewed. RESULTS: "Dense" ERMs were seen with abundant clusters of fibrous long-spacing collagen embedded in compactly folded native vitreous collagen strands. Posterior hyaloids were attached to the retina in the majority of cases. Both groups of ERMs showed positive immunoreactivity for glial fibrillic acidic protein and hyalocyte markers. Anti-α-smooth muscle actin labeling was most positive in "tractional" ERMs. Surgery resulted in significant improvement (74%) of visual acuity, with a mean gain of 2 Snellen lines in both groups. All other patients (26%) preserved vision. Three patients (16%) developed a full-thickness macular defect requiring additional surgery. CONCLUSIONS: Morphologic components differ in epiretinal cell proliferations of LMHs. In association with degradation of vitreous collagen, glial cells and hyalocytes seem to play an important role in LMH development. Since functional benefit after surgery was limited and progression to a full-thickness macular defect was a notable complication, we recommend caution in proceeding with surgical intervention. Further investigations are needed to elucidate whether "dense" and "tractional" LMHs represent different disease entities or different stages of one disorder.

Early perfusion of a free RPE-choroid graft in patients with exudative macular degeneration can be imaged with spectral domain-OCT.

PURPOSE: To study early flow and revascularization in a free, autologous, retinal pigment epithelium (RPE)-choroid graft. METHODS: This prospective cohort study used spectral domain-optical coherence tomography (SD-OCT) after RPE-choroid graft surgery in 12 patients. This SD-OCT was combined with fluorescein angiography (FA) and indocyanine green angiography (ICGA) in 5 patients. RESULTS: SD-OCT revealed that vessel diameter, number of vessels, and graft thickness increased in 10 of 12 patients, starting between 3 and 10 days after surgery. A subsequent decrease in thickness was found in all 10 patients, beginning as early as 8 days after surgery. Initially, the graft vessels were optically clearer than the underlying choroidal recipient vessels. Between 8 and 30 days after surgery, the optically clear vessels became gray, similar to the recipient choroid. FA and ICGA revealed perfusion in 4 of 5 patients between postoperative days 6 and 15. Between postoperative days 12 and 60, the entire choroidal structure of the graft was visible on ICGA. CONCLUSIONS; These data suggest that enlargement of vessel diameter, increase in the number of choroidal vessels, and graft thickening visualized by SD-OCT correspond with the ingrowth of afferent vessels, as demonstrated by ICGA. The subsequent establishment of efferent vessels results in flow, imaged as a change in color of the graft's vessels from optically clear to gray, graft thinning on SD-OCT, and complete revascularization on ICGA. SD-OCT, a noninvasive examination, can be used to demonstrate early graft perfusion in patients (trialregister.nl/trialreg/admin/rctview.asp number, NTR1768).

Postoperative complications and intraocular pressure in 943 consecutive cases of 23-gauge transconjunctival pars plana vitrectomy with 1-year follow-up.

BACKGROUND: To report the rate of postoperative complications in 943 consecutive eyes operated on with 23-gauge transconjunctival pars plana vitrectomy. METHODS: Single-center, retrospective, noncomparative, interventional case series. Nine hundred and forty-three eyes underwent 23-gauge transconjunctival core and peripheral vitrectomy with peripheral laser at the sclerotomy sites from May 2005 through April 2008. The main outcome measures were intraocular pressure at 1 day and at 1 week and intra- and postoperative complications with at least 6-month follow-up. RESULTS: Eight hundred and thirty-one eyes (88%) did not have either significant intra- or postoperative complications. Sclerotomy leakage requiring suture occurred in 37 eyes (3.9%). One choroidal detachment (0.1%) spontaneously resolved 1 week after surgery. At postoperative Day 1, 31 eyes (3.3%) experienced transient hypotony. Forty-five eyes (4.8%) presented a subtle vitreous hemorrhage that resolved spontaneously. Two retinal detachments (0.2%) occurred, one at 1 month and one at 3 months. They resolved with one further vitrectomy. Seven hundred and forty eyes completed the 12-month follow-up and presented no further complications. CONCLUSION: Twenty-three-gauge complete vitrectomy and peripheral laser seem safe for a variety of vitreoretinal surgical procedures. The rate of post- and intraoperative complications compares favorably with 25-gauge and with the standard 20-gauge vitrectomy.