FROM OUTER RETINAL NEOVACULARIZATION TO EXUDATIVE SUBRETINAL NEOVASCULARIZATION IN MACULAR TELANGIECTASIA TYPE 2.

PURPOSE: To describe the progression from outer retinal neovascularization (ORNV) to exudative subretinal new vessels (SRNVs) in idiopathic macular telangiectasia type 2. METHODS: A total of 135 patients (270 eyes) imaged with optical coherence tomography angiography were included. MAIN OUTCOME MEASURES: Ellipsoid zone loss, outer retinal hyperreflectivity, ORNV, and SRNVs. Outer retinal neovascularization was defined as a flow signal passing through the outer plexiform layer, with or without vertical linear outer retinal hyperreflectivity on the optical coherence tomography B-scan. Subretinal new vessels were defined as an abnormal capillary network with a peripheral anastomotic arcade seen on en face optical coherence tomography angiography and a convex hyperreflectivity at the retinal pigment epithelium. RESULTS: Subretinal new vessels were observed in 38/270 eyes (14%). Subretinal new vessels were at a fibrotic stage in 24/38 eyes and at an exudative stage in 6/38 eyes, and a progression from ORNV to SRNVs was documented in 8/38 eyes. All cases showed an ellipsoid zone loss. In seven eyes (2.5%), SRNVs were also associated with subepithelial neovascularization. No retinochoroidal anastomosis was detected. The visual acuity dropped when SRNVs were present. CONCLUSION: In this case series, SRNVs were found in 14% of eyes. In all cases, they were associated with an ellipsoid zone loss and with outer retinal hyperreflectivity. A progression from ORNV to SRNVs was observed.

ABNORMALITIES IN THE RETINAL CAPILLARY PLEXUSES IN COATS DISEASE IN ADULTHOOD ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To describe and quantify the abnormalities of the retinal capillary plexuses using optical coherence tomography angiography in Coats disease. METHODS: Retrospective study. Eleven eyes of 11 patients with Coats disease (9 men and two women aged 32-80 years) compared with nine fellow eyes and 11 healthy control eyes. Horizontal bands of contiguous 3 × 3 mm optical coherence tomography angiograms of the superficial vascular plexus and deep capillary complex were acquired from the optic disk to 6 mm temporal to the fovea, through areas with telangiectasia visible on fluorescein angiography in 9 cases. RESULTS: The vascular density was significantly decreased in both plexuses in eyes with Coats disease compared with normal and fellow eyes within the 6 mm temporal to the fovea (superficial vascular plexus: 21.5 vs. 29.4%, P = 0.00004 and vs. 30.3%, P = 0.00008; deep capillary complex, 16.5 vs. 23.9%, P = 0.00004 and vs. 24.7%, P = 0.00008, respectively). The fractal dimension was also significantly decreased in eyes with Coats disease (superficial vascular plexus: 1.796 vs. 1.848 P = 0.001 and vs. 1.833, P = 0.003; deep capillary complex: 1.762 vs. 1.853, P = 0.003 and vs. 1.838, P = 0.004, respectively). CONCLUSION: Retinal plexuses' vascular density was decreased in Coats disease, including in areas with no visible telangiectasia.

INTRARETINAL HYPERREFLECTIVE LINES.

PURPOSE: To report intraretinal hyperreflective lines related to various macular conditions. METHODS: All cases were imaged with color photographs, autofluorescence images, and spectral-domain optical coherence tomography, some with fluorescein and/or indocyanine green angiography. Demographic data, imaging, course and outcome were retrospectively analyzed. RESULTS: Forty-nine eyes of 43 patients (16 men and 27 women) were included. Hyperreflective vertical lines (38 eyes) or curvilinear lines along the Henle fiber layer (11 eyes) were present in association with various macular conditions: adult vitelliform dystrophy or pattern dystrophy (24 eyes) frequently associated with an epiretinal membrane (six eyes) and/or thick choroid (nine eyes), age-related maculopathy or macular degeneration (nine eyes), partial resorption of subretinal or intraretinal hemorrhages (five eyes), idiopathic macular microhole (two eyes), vitreomacular traction (three eyes), multiple evanescent white dot syndrome (three eyes), fundus flavimaculatus (two eyes), and pachychoroid pigment epitheliopathy (one eye). The lines fully vanished in cases of hemorrhages, multiple evanescent white dot syndrome or resolution of vitreomacular traction, but usually persisted with gradual thinning in the other conditions. CONCLUSION: The present series showed that intraretinal hyperreflective lines could occur in various inflammatory, degenerative, or tractional conditions. They could reflect a previously unrecognized reaction to various photoreceptor, Müller cell, and/or retinal pigment epithelium damage.

Consensus Nomenclature for Reporting Neovascular Age-Related Macular Degeneration Data: Consensus on Neovascular Age-Related Macular Degeneration Nomenclature Study Group.

PURPOSE: To establish a process to evaluate and standardize a state-of-the-art nomenclature for reporting neovascular age-related macular degeneration (AMD) data. DESIGN: Consensus meeting. PARTICIPANTS: An international panel of retina specialists, imaging and image reading center experts, and ocular pathologists. METHODS: During several meetings organized under the auspices of the Macula Society, an international study group discussed and codified a set nomenclature framework for classifying the subtypes of neovascular AMD and associated lesion components. MAIN OUTCOME MEASURES: A consensus classification of neovascular AMD. RESULTS: The study group created a standardized working definition of AMD. The components of neovascular AMD were defined and subclassified. Disease consequences of macular neovascularization were delineated. CONCLUSIONS: The framework of a consensus nomenclature system, a definition of AMD, and a delineation of the subtypes of neovascular AMD were developed. Establishing a uniform set of definitions will facilitate comparison of diverse patient groups and different studies. The framework presented is modified and updated readily, processes that are anticipated to occur on a periodic basis. The study group suggests that the consensus standards outlined in this article be used in future reported studies of neovascular AMD and clinical practice.

RAPID MACULAR CAPILLARY LOSS IN PATIENTS WITH UNCONTROLLED TYPE 1 DIABETES.

PURPOSE: To analyze the evolution of macular vessel density (VD) over 1 year, during early worsening of diabetic retinopathy, in patients with uncontrolled Type 1 diabetes (T1D). METHODS: Retrospective study of 12 eyes of 9 patients with T1D with early worsening of diabetic retinopathy imaged with optical coherence tomography angiography. The following data were collected at the time of pan retinal photocoagulation initiation and after 6 and 12 months: vessel density within three retinal plexuses-superficial vascular plexus, intermediate capillary plexus, and deep capillary plexus; foveal avascular zone area, acircularity index, and flow density (FD)-300; central macular thickness; and HbA1c levels. RESULTS: A history of rapid reduction in blood glucose was found in seven of nine cases. Vessel density was significantly decreased at 12 months in all plexuses: from 44.68 ± 4.75 to 40.23 ± 7.13 in the superficial vascular plexus (P = 0.008), from 42.72 ± 4.86 to 37.12 ± 8.64 in the intermediate capillary plexus (P = 0.03), and from 22.68 ± 3.93 to 19.66 ± 4.92 in the deep capillary plexus (P = 0.004). Intermediate capillary plexus and deep capillary plexus changes were strongly correlated (r = 0.86, P < 0.001) and were significant as early as 6 months. The mean foveal avascular zone area increased (P = 0.05) and the FD-300 decreased (P = 0.03). No significant change in acircularity index, central macular thickness, and visual acuity were observed over time. CONCLUSION: Early worsening of diabetic retinopathy induces a rapid macular capillary dropout mainly affecting the intermediate capillary plexus and deep capillary plexus.

Serous Retinal Detachment in Dome-Shaped Macula Is Associated with Greater Central Choroidal Blood Flow Measured by Optical Coherence Tomography Angiography.

PURPOSE: Dome-shaped macula (DSM) is characterized by an inward bulge in the macula, often associated with a myopic staphyloma. One complication of DSM is particularly studied: foveolar serous retinal detachment (SRD). This study analyzed the variations of optical coherence tomography angiography (OCT-A) decorrelation signal in cases of DSM with and without SRD. METHODS: This was a retrospective study including twenty height eyes presenting with DSM. OCT-A scans were recorded, and the intensity of the choroidal decorrelation signal was quantified to analyze choroidal blood flow (CBF) in central, temporal, and nasal macular areas. The size of retinal pigment epithelium (RPE) atrophy was evaluated. RESULTS: CBF in the central area was significantly greater in the SRD group than in the no-SRD group (7.00 × 105 vs. 2.58 × 105) (p = 0.0049). CBF appeared decreased in the subfoveal area compared with the periphery for patients without SRD (p = 0.0107). The size of RPE atrophy was 0.762 optic disc area ±0.87. RPE atrophy correlated very significantly with CBF (p = 0.0012). CONCLUSION: A greater retrofoveolar CBF intensity is associated with the presence of SRD. These changes could reflect variations of CBF, and may represent a potential explanation for the pathogenesis of SRD in DSM.

Widefield OCT-Angiography and Fluorescein Angiography Assessments of Nonperfusion in Diabetic Retinopathy and Edema Treated with Anti-Vascular Endothelial Growth Factor.

PURPOSE: To assess change in retinal nonperfusion (NP) after anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME) using 2 different imaging modalities: swept-source widefield (SS-WF) OCT angiography (OCTA) and ultra-widefield (UWF) fluorescein angiography (FA). DESIGN: Observational case series. PARTICIPANTS: Ten eyes of 9 patients with severe nonproliferative diabetic retinopathy (NPDR) or proliferative DR (PDR) initiating 3 monthly anti-VEGF intravitreal injections for DME. METHODS: All eyes were imaged with UWF color fundus photographs (CFPs), UWF FA, and SS-WF OCTA at baseline (M0) and 1 month after the third anti-VEGF injection (M3). All images were aligned and divided into 16 boxes for analysis of NP areas by 2 blinded retina specialists. MAIN OUTCOME MEASURES: The number of discrepancies between SS-WF OCTA and UWF FA regarding the detection of NP areas and small vessels passing through NP areas; assessment of DR severity on UWF CFP; and change in each NP area between M0 and M3: number of boxes/eye with presence of at least 1 NP area, number of arterioles or venules that disappeared or reappeared, and number of NP areas in which capillaries disappeared or reappeared. RESULTS: The diabetic retinopathy (DR) severity score improved by at least 1 stage in 8 of 10 eyes, with a significant decrease in the mean number of microaneurysms and retinal hemorrhages on UWF CFP at M3 versus M0 (n = 40±28 vs. 121±57; P = 0.0020) and regression of fundus neovascularization when present. All NP areas detected on FA were seen on SS-WF OCTA, but additional NP areas were detected on SS-WF OCTA at M0 in 29% (46/160) of boxes. No reperfusion of arterioles or venules was observed at M3 on FA or SS-WF OCTA. Retinal capillaries were only visible on OCTA, and no reperfusion in NP areas was observed even when a reduction in dark areas was visible on FA. CONCLUSIONS: No reperfusion of vessels or capillary network was detected in NP areas using 2 imaging techniques, UWF FA and SS-WF OCTA, in eyes with DR after 3 anti-VEGF injections. The detection rate of NP areas was higher with SS-WF OCTA than with UWF FA.

VESSEL DENSITY OF SUPERFICIAL, INTERMEDIATE, AND DEEP CAPILLARY PLEXUSES USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To provide values of retinal vessel density (VD) in the three retinal capillary plexuses, foveal avascular zone (FAZ) area, and retinal layer thickness in a cohort of healthy subjects. METHODS: The optical coherence tomography angiography maps of 148 eyes of 84 healthy subjects, aged 22 to 76 years, were analyzed for measuring VD of the retinal capillary plexuses, using the Optovue device comprising a projection artifact removal algorithm. Foveal avascular zone metrics were measured, and the relationship between optical coherence tomography angiography findings and age, sex, and image quality was studied. RESULTS: The deep capillary plexus showed the lowest VD (31.6% ± 4.4%) in all macular areas and age groups compared with the superficial vascular plexus (47.8% ± 2.8%) and intermediate capillary plexus (45.4% ± 4.2%). The mean VD decreased by 0.06%, 0.06%, and 0.08% per year, respectively, in the superficial vascular plexus, intermediate capillary plexus, and deep capillary plexus. Mean FAZ area, FAZ acircularity index, and capillary density in a 300-µm area around the FAZ were 0.25 ± 0.1 mm, 1.1 ± 0.05, and 50.8 ± 3.4%, respectively. The yearly increase in FAZ area was 0.003 mm (P < 0.001). CONCLUSION: The deep capillary plexus, a single monoplanar capillary plexus located in the outer plexiform layer, has the lowest VD, a significant finding that might be used to evaluate retinal vascular diseases. Vascular density decreased with age in the three capillary plexuses.

OPTICAL COHERENCE TOMOGRAPHY, FLUORESCEIN ANGIOGRAPHY, AND DIAGNOSIS OF CHOROIDAL NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To determine the sensitivity and specificity of different retinal imaging combinations for the diagnosis of choroidal neovascularization (CNV) in age-related macular degeneration. METHODS: Patients aged 50 years or older referred for suspicious recent-onset CNV related to age-related macular degeneration were prospectively included for 6 months. Data recorded included color fundus photographs (CFPs), spectral domain optical coherence tomography (SD-OCT), and fluorescein angiography (FA) images. Five retina specialists randomly interpreted SD-OCT combined with CFP, and then FA combined with CFP. The reference diagnosis of CNV was based on the agreement of two readers in the interpretation of the SD-OCT + FA + CFP combination. RESULTS: One hundred and forty-eight patients (148 eyes) were included. For the diagnosis of CNV, the sensitivity of both SD-OCT + CFP and FA + CFP was of 90.9%. Type 2 CNV was diagnosed in 98% to 100% of cases with SD-OCT + CFP or FA + CFP, whereas Type 1 CNV was diagnosed in 82.9% of cases with SD-OCT + CFP and 81.6% with FA + CFP. CONCLUSION: When used as a first diagnostic test, SD-OCT combined with CFP had sensitivity and specificity similar to those of FA combined with CFP, for the diagnosis of CNV in age-related macular degeneration. This shows the increasingly important role of SD-OCT as a first-line test in the diagnosis of CNV.

ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY CAN IMPROVE DIABETIC RETINOPATHY SCORE WITHOUT CHANGE IN RETINAL PERFUSION.

PURPOSE: To compare the changes in retinal perfusion on ultra-wide-field fluorescein angiography with the changes in diabetic retinopathy lesions observed on ultra-wide-field fundus color photographs after 3 monthly anti-vascular endothelial growth factor injections. METHODS: Retrospective interventional cohort study analyzing the files of 14 patients with DR (18 eyes). UWF color photos and FA were analyzed at baseline (M0) and 1 month after the third anti-VEGF injection (M3). The main outcomes included the count of the number of red dots (microaneurysms, hemorrhages) and assessment of DR severity score (DRSS); the analysis of non-perfusion areas and disappearance or reappearance of arterioles or venules in the non-perfusion areas on FA. RESULTS: Eighteen eyes of 14 diabetic patients, with mean age of 63 ± 5 years, were included. The DRSS score improved by at least one stage in 11/18 (61%) eyes. The mean number of red dots significantly decreased at M3 (n = 80 ± 85) compared with M0 (n = 139 ± 130) (P < 0.0001). No reperfusion of arterioles or venules was observed in or around nonperfusion areas. CONCLUSION: After anti-vascular endothelial growth factor injections, the improvement in the DRSS score based on color fundus photographs can occur without retinal reperfusion on ultra-wide-field fluorescein angiography.

MANAGEMENT OF RETINAL HEMANGIOBLASTOMA IN VON HIPPEL-LINDAU DISEASE.

PURPOSE: To review the current state of diagnosis and management of retinal hemangioblastoma and retinal vascular proliferation arising from von Hippel-Lindau (VHL) disease. METHODS: A review of the literature was performed. Consensus was reached among authors regarding current practice, with reference to published data where possible. RESULTS: von Hippel-Lindau disease and its ocular manifestations are relatively rare, and there is limited evidence in the literature on which to base management. There was consensus on core principles, including 1) recognition and diagnosis of von Hippel-Lindau disease when present, with appropriate referral for care of this potentially lethal systemic condition; 2) regular ophthalmic evaluation for individuals with von Hippel-Lindau disease, to identify and offer timely treatment for new or active retinal hemangioblastomas; 3) ablative treatment of retinal hemangioblastomas that can be safely destroyed, to lower risk of vision loss; 4) observation or consideration of nonablative treatments for retinal hemangioblastomas that cannot be safely destroyed; and 5) observation of asymptomatic retinal vascular proliferation, with consideration of vitrectomy for lesions exerting effects on vision. CONCLUSION: Ocular outcomes can be gratifying in many cases with appropriate management. Improved understanding of the molecular basis for the disease creates an opportunity for rational design of better therapies.

VON HIPPEL-LINDAU DISEASE: Update on Pathogenesis and Systemic Aspects.

PURPOSE: To provide an update summarizing the biologic pathways governing von Hippel-Lindau (VHL) disease pathogenesis and to provide an overview of systemic manifestations as well as screening recommendations. METHODS: A PubMed search of the English language literature was reviewed using the following search terms: von Hippel-Lindau, von Hippel-Lindau disease, and VHL. Of 6,696 publications, the most current and pertinent information related to the pathogenesis and systemic aspects of VHL disease were included in this review. RESULTS: von Hippel-Lindau disease is one of the most frequently occurring multisystem familial cancer syndromes. The disease results from germline mutation in the VHL tumor suppressor gene on the short arm of chromosome 3. Mutation in the VHL gene affects multiple cellular processes including transcriptional regulation, extracellular matrix formation, apoptosis, and, in particular, the cellular adaptive response to hypoxia. As a result, there is widespread development of vascular tumors affecting the retina, brain, and spine, as well as a spectrum of benign and malignant tumors and/or cysts in visceral organs. CONCLUSION: The ophthalmologist plays a key role in VHL disease diagnosis, as retinal hemangioblastoma is frequently the first disease manifestation. Screening guidelines for individuals with known VHL disease, and those at risk of VHL disease, help to ensure early detection of potentially vision-threatening and life-threatening disease.

A dominant mutation in MAPKAPK3, an actor of p38 signaling pathway, causes a new retinal dystrophy involving Bruch's membrane and retinal pigment epithelium.

Inherited retinal dystrophies are clinically and genetically heterogeneous with significant number of cases remaining genetically unresolved. We studied a large family from the West Indies islands with a peculiar retinal disease, the Martinique crinkled retinal pigment epitheliopathy that begins around the age of 30 with retinal pigment epithelium (RPE) and Bruch's membrane changes resembling a dry desert land and ends with a retinitis pigmentosa. Whole-exome sequencing identified a heterozygous c.518T>C (p.Leu173Pro) mutation in MAPKAPK3 that segregates with the disease in 14 affected and 28 unaffected siblings from three generations. This unknown variant is predicted to be damaging by bioinformatic predictive tools and the mutated protein to be non-functional by crystal structure analysis. MAPKAPK3 is a serine/threonine protein kinase of the p38 signaling pathway that is activated by a variety of stress stimuli and is implicated in cellular responses and gene regulation. In contrast to other tissues, MAPKAPK3 is highly expressed in the RPE, suggesting a crucial role for retinal physiology. Expression of the mutated allele in HEK cells revealed a mislocalization of the protein in the cytoplasm, leading to cytoskeleton alteration and cytodieresis inhibition. In Mapkapk3-/- mice, Bruch's membrane is irregular with both abnormal thickened and thinned portions. In conclusion, we identified the first pathogenic mutation in MAPKAPK3 associated with a retinal disease. These findings shed new lights on Bruch's membrane/RPE pathophysiology and will open studies of this signaling pathway in diseases with RPE and Bruch's membrane alterations, such as age-related macular degeneration.

ACUTE PSEUDOPHAKIC CYSTOID MACULAR EDEMA IMAGED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To study macular capillary changes and vessel density in acute pseudophakic cystoid macular edema (PCME) before and after treatment using optical coherence tomography angiography. METHODS: Retrospective observational case-control study of seven consecutive patients (eight eyes) with PCME and eight age-matched control eyes imaged with optical coherence tomography angiography (RTVue XR Avanti; Optovue, Inc, Fremont, CA) using Projection Removal Artifacts software. Vessel density was calculated. RESULTS: The mean time to diagnosis of PCME was 2.3 ± 0.9 months after surgery. At initial examination, the superficial capillary plexus pattern was near-normal in all PCME eyes, although it was attenuated in the deep capillary plexus. The mean vessel density of the superficial capillary plexus in PCME eyes was slightly but significantly lower than in control eyes (47.8 ± 3.8% vs. 52.9 ± 4.0%, P = 0.01), the difference being greater in the deep capillary plexus (44.1 ± 7.4% vs. 54.2 ± 3.2%, P = 0.007). After resolution of the edema, the deep capillary plexus completely recovered its normal pattern and the vessel density in both plexuses was no longer different from that observed in control eyes. CONCLUSION: Macular vessel density after resolution of an acute PCME did not differ from that of normal control eyes in both the superficial capillary plexus and deep capillary plexus, unlike macular edema in retinal vaso-occlusive diseases.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF FLAT IRREGULAR PIGMENT EPITHELIUM DETACHMENT IN CHRONIC CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To assess the rate of choroidal neovascularization (CNV) detected by optical coherence tomography angiography (OCTA) in flat irregular pigment epithelium detachment (PED) in chronic central serous chorioretinopathy. METHODS: Data on all consecutive patients with chronic central serous chorioretinopathy who underwent OCTA over a 1-year period were reviewed. The presence of flat irregular PED, which was defined as an irregular elevation of the retinal pigment epithelium allowing the visualization of a distinct Bruch's membrane was assessed on high-resolution OCT B-scan. Clinical, multimodal imaging, and OCTA data were reviewed by two graders for the detection of CNV. RESULTS: Eighty-eight eyes of 61 patients with chronic central serous chorioretinopathy were included. Patient mean age (±SD) was 54.5 ± 12.2 years, and 78.7% were males. Mean subfoveal choroidal thickness (±SD) was 452.6 ± 145.6 µm. Flat irregular PEDs were detected in 59 eyes of 51 patients. OCTA detected the presence of CNV in flat irregular PEDs in 35.6% of cases. Conversely, using the combination of spectral domain optical coherence tomography angiography, fluorescein and indocyanine green angiography, CNV was detected in only 25% of flat irregular PEDs. All hyporeflective flat irregular PEDs on OCT were avascular on OCTA while they were at least partially hyperreflective when associated with CNV. CONCLUSION: One-third of flat irregular PEDs in chronic central serous chorioretinopathy contained CNV. OCTA detected CNV more frequently than the other imaging modalities. Further longitudinal studies are needed to assess the indication of antivascular endothelial growth factor treatments in such cases.

Incidence of Macular Holes in the Fellow Eye without Vitreomacular Detachment at Baseline.

PURPOSE: To determine the rate of macular holes (MH) occurring in the fellow eyes of eyes with MH depending on the vitreomacular interface at baseline. METHODS: This was a retrospective study of patients operated on for idiopathic MH, with persistent vitreofoveal attachment in the fellow eye assessed by spectral-domain optical coherence tomography (SD-OCT). Follow-up lasted 6 months or more, and the main outcome was the occurrence of an MH. RESULTS: The 77 fellow eyes included had a mean follow-up of 34.11 ± 22.3 months (6-78.4). At baseline, 31 eyes had vitreomacular traction (VMT), 35 vitreomacular adhesion, and 11 no posterior vitreous detachment. MH occurred in 19.5% of the cases (15/77). The rate of MH was significantly higher among the eyes with VMT than among the eyes without VMT at baseline (35.5 vs. 8.7%; p = 0.009). CONCLUSION: One-third of eyes with VMT at baseline identified by SD-OCT will develop an MH in the following 5 years.

Martinique Crinkled Retinal Pigment Epitheliopathy: Clinical Stages and Pathophysiologic Insights.

PURPOSE: To reappraise the autosomal dominant Martinique crinkled retinal pigment epitheliopathy (MCRPE) in light of the knowledge of its associated mutated gene mitogen-activated protein kinase-activated protein kinase 3 (MAPKAPK3), an actor in the p38 mitogen-activated protein kinase pathway. DESIGN: Clinical and molecular study. PARTICIPANTS: A total of 45 patients from 3 generations belonging to a family originating from Martinique with an autosomal dominant MCRPE were examined. METHODS: Best-corrected visual acuity, fundus photographs, and spectral-domain optical coherence tomography (SD OCT) of all clinically affected patients and carriers for the causal mutation were reviewed at the initial visit and 4 years later for 10 of them. Histologic retinal lesions of Mapkapk3(-/-) mice were compared with those of the human disease. MAIN OUTCOME MEASURES: The MCRPE natural history in view of MAPKAPK3 function and Mapkapk3(-/-) mouse retinal lesions. RESULTS: Eighteen patients had the c.518T>C mutation. One heterozygous woman aged 20 years was asymptomatic with normal fundus and SD OCT (stage 0). All c.518T>C heterozygous patients older than 30 years of age had the characteristic dried-out soil fundus pattern (stages 1 and 2). Complications (stage 3) were observed in 7 cases, including polypoidal choroidal vasculopathy (PCV) and macular fibrosis or atrophy. One patient was homozygous and had a form with severe Bruch's membrane (BM) thickening and macular exudation with a dried-out soil pattern in the peripheral retina. The oldest heterozygous patient, who was legally blind, had peripheral nummular pigmentary changes (stage 4). After 4 years, visual acuity was unchanged in 6 of 10 patients. The dried-out soil elementary lesions radically enlarged in patients with a preferential macular extension and confluence. These findings are in line with the progressive thickening of BM noted with age in the mouse model. During follow-up, there was no occurrence of PCV. CONCLUSIONS: MCRPE is an autosomal dominant, fully penetrant retinal dystrophy with a preclinical stage, an onset after the age of 30 years, and a preserved visual acuity until occurrence of macular complications. The natural history of MCRPE is in relation to the role of MAPKAPK3 in BM modeling, vascular endothelial growth factor activity, retinal pigment epithelial responses to aging, and oxidative stress.

CONE DENSITY LOSS ON ADAPTIVE OPTICS IN EARLY MACULAR TELANGIECTASIA TYPE 2.

PURPOSE: To determine whether cone photoreceptors are impaired early in macular telangiectasia type 2 (MacTel 2) progression. METHODS: Eight patients with MacTel 2 lacking intraretinal cavitation underwent multimodal retinal imaging including adaptive optics. Cone packing metrics were determined in 5 sampling windows at different eccentricities from the fovea. Results were compared with a previously established normative database. RESULTS: In MacTel 2 eyes, cone density was significantly lower than normal at all eccentricities (P < 0.0001). Mean cone spacing and mean percentage of hexagonally organized cone photoreceptors were respectively significantly larger and lower than normal at all eccentricities (P = 0.0488 and P < 0.0001). In MacTel 2 patients, adaptive optics showed an irregular patchy disturbance of the cone mosaic corresponding to some fragmentation of the interdigitation zone on optical coherence tomography. The ellipsoid zone remained intact in the studied area. CONCLUSION: Adaptive optics showed that the macular cone density was lower than normal even outside the telangiectasia in MacTel 2 lacking intraretinal cavitation, although the ellipsoid zone remained intact on optical coherence tomography. These findings do not indicate that the cone density loss is causative of the disease as it might be secondary to Müller cell or rod loss in this area. However, cone density assessment could become a useful parameter to monitor disease progression.

CORRELATION BETWEEN CYSTOID SPACES IN CHRONIC DIABETIC MACULAR EDEMA AND CAPILLARY NONPERFUSION DETECTED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To study the relationship between the location of cystoid spaces and retinal capillary nonperfusion areas in diabetic cystoid macular edema (DCME). METHODS: In this retrospective study, 24 eyes of 21 patients with chronic DCME were followed using optical coherence tomography angiography. The capillary density of the superficial capillary plexus and deep capillary plexus was measured using AngioAnalytics software in all DCME eyes and in 20 healthy controls. Diabetic cystoid macular edema improved spontaneously or after treatment in 11 eyes. RESULTS: The intraretinal cystoid spaces were surrounded by capillary-flow void areas in the superficial capillary plexus in 71% of cases and in the deep capillary plexus in 96% of cases. The deep capillary plexus had lost its regular pattern in all cases. The capillary density was decreased in both plexus (mean decrease of -23.0% in the superficial capillary plexus and -12.4% in the deep capillary plexus vs. normal). In the 11 cases with DCME resolution, the capillary did not reperfuse in areas of resolved cystoid spaces, and the capillary density did not change significantly. CONCLUSION: In chronic DCME, cystoid spaces were located within capillary dropout areas. No reperfusion occurred after DCME resolution. The impact of the severity of this nonperfusion on the risk of recurrence of DCME remains to be clarified.

LONG-TERM EVOLUTION OF DOME-SHAPED MACULA: Increased Macular Bulge is Associated With Extended Macular Atrophy.

PURPOSE: Dome-shaped macula (DSM) may cause impaired vision. This study analyzed the long-term evolution of DSM, most particularly macular changes: serous retinal detachment, retinal pigment epithelium atrophy, and DSM bulge increase. METHODS: Twenty-nine eyes presenting with DSM were retrospectively studied. Clinical data, color photographs, fluorescein angiographs, and optical coherence tomography examinations were reviewed. Patients were followed up from 6 months to 111 months (mean, 37.89 months). The height of the macular bulge, the size of retinal pigment epithelium macular atrophy, and serous retinal detachment progression were studied. Other macular changes were noted. RESULTS: Mean vision remained stable. Dome-shaped macula height increased significantly from 338.9 µm to 364.3 µm (P = 0.007). Serous retinal detachment was present initially in 15 of 29 eyes; it increased in 4 cases and resolved spontaneously in 7. Macular retinal pigment epithelium atrophy correlated with the bulge height (P = 0.015), and it enlarged during follow-up (1.12 vs. 1.34, P = 0.04). Other macular anomalies were present initially or appeared during follow-up: macular pucker, choroidal neovascularization (CNV), subretinal pigmentary clumps, and flat irregular pigmented epithelium detachment. A few treatments were proven in serous retinal detachment cases but were ineffective in restoring vision. CONCLUSION: In DSM, vision may be stable for years while macular changes progress: the macular bulge increases as does retinal pigment epithelium atrophy.