Faculty Bibliography

OBJECTIVE: To evaluate the clinical outcomes after vitrectomy with inner retinal fenestration-making a partial thickness retinal hole radial to the pit-for the treatment of optic disc pit maculopathy. DESIGN: Retrospective, interventional case series. PARTICIPANTS: Eighteen eyes with optic disc pit maculopathy. INTERVENTION: Pars plana vitrectomy with creation of an inner retinal fenestration was performed in all eyes. A bent 25-gauge needle was used to make a partial thickness inner retinotomy just temporal to the optic disc pit. MAIN OUTCOME MEASURES: Anatomic outcomes determined by optical coherence tomography and postoperative best-corrected visual acuity (BCVA). RESULTS: Before surgery, gross thickening of the inner and outer retinal layers with accumulation of fluid in the central macula was present in all eyes. Macular detachment was observed in 14 eyes, and outer layer hole was identified in 9 eyes. Patients were followed up for a mean of 34.6+/-26.6 months after surgery. After surgery, complete resolution of fluid in and under the fovea was achieved in 17 eyes (94%) without additional treatment. In these eyes, reduction of the inner retinal fluid was followed by a slow decrease in the outer retinal fluid and macular detachment. The macular detachment resolved in a mean of 6.1+/-3.9 months after surgery. Postoperative BCVA (mean, 0.378+/-0.487 logarithm of the minimum angle of resolution [logMAR]; Snellen equivalent, 20/48) improved significantly compared with preoperative BCVA (mean, 0.725+/-0.510 logMAR; Snellen equivalent, 20/106; P = 0.006). Ten eyes (56%) had a postoperative BCVA of 20/30 or better. There was neither the recurrence of macular detachment nor an accumulation of outer retinal fluid in the central macula in any eyes. CONCLUSIONS: The introduction of a partial thickness fenestration radial to the optic disc pit was associated with retinal anatomic and functional improvement without additional treatments. These results are consistent with the hypothesis that redirection of flow to allow egress of fluid into the vitreous cavity instead of into the retina can achieve long-lasting amelioration of the pathologic findings of optic pit maculopathy.

IMPORTANCE Optical coherence tomography (OCT) abnormalities of age-related macular degeneration (AMD) have not been fully characterized because of the complex morphology and a lack of correlative histologic studies. Expansion of our ability to interpret increasing attributes brings us closer to the goal of in vivo histologic analysis of the eye by OCT. OBJECTIVE To describe a new outer retinal finding of AMD using spectral-domain (SD) OCT and suggest histopathologic correlates. DESIGN, SETTING, AND PARTICIPANTS Twenty-five eyes of 16 patients with AMD with severe atrophy due to either choroidal neovascularization (CNV) or geographic atrophy (GA) and 53 donor eyes of 53 patients with late AMD were included. Imaging studies were conducted at a referral retinal practice and histopathology was done at a university research laboratory. EXPOSURES Findings in the outer retina were evaluated in SD-OCT images in eyes with atrophy of the retinal pigment epithelium (RPE) and compared with histopathologic findings in eyes with GA or CNV that also showed loss of the RPE. MAIN OUTCOMES AND MEASURES Spectral-domain OCT and histologic characteristics of the outer retina. RESULTS The mean (SD) age of the 16 patients was 82.7 (7.9) years. Twenty eyes had CNV and 5 eyes had GA. The mean best-corrected visual acuity was 0.800 logMAR (interquartile range, 0.350-1.000 logMAR), a Snellen equivalent of 20/126. A curvilinear hyperreflective density was identified above the Bruch membrane line within the atrophic area in the SD-OCT images. At the internal border, the material was contiguous with the outer portion of the RPE band. Below the material was a relatively hyporeflective space. The material was thrown into folds in cases with atrophy following CNV or was seen as a sheet with numerous bumps in eyes with GA. Review of histopathologic findings of eyes with advanced GA and CNV revealed a rippled layer of basal laminar deposits in an area of RPE atrophy that was located in the same level as the curvilinear line seen in the OCT images. CONCLUSIONS AND RELEVANCE We have described a new entity, termed outer retinal corrugations, which may correspond to histological findings of basal laminar deposits, extracellular deposits that persist in eyes with late AMD. Observation of this undulating band does not necessarily mean there is exudation or leakage; as a consequence, these patients do not need treatment based on this solitary finding.

PURPOSE: To develop a consensus nomenclature for the classification of retinal and choroidal layers and bands visible on spectral-domain optical coherence tomography (SD-OCT) images of a normal eye. DESIGN: An international panel with expertise in retinal imaging (International Nomenclature for Optical Coherence Tomography [IN*OCT] Panel) was assembled to define a consensus for OCT imaging terminology. PARTICIPANTS: A panel of retina specialists. METHODS: A set of 3 B-scan images from a normal eye was circulated to the panel before the meeting for independent assignment of nomenclature to anatomic landmarks in the vitreous, retina, and choroid. The outputs were scrutinized, tabulated, and used as the starting point for discussions at a roundtable panel meeting. The history of anatomic landmark designations over time was reviewed for the various cellular layers of the ocular structures that are visible by SD-OCT. A process of open discussion and negotiation was undertaken until a unanimous consensus name was adopted for each feature. MAIN OUTCOME MEASURES: Definitions of normal eye features showed by SD-OCT. RESULTS: Definitions for various layers changed frequently in the literature and were often inconsistent with retinal anatomy and histology. The panel introduced the term "zone" for OCT features that seem to localize to a particular anatomic region that lacks definitely proven evidence for a specific reflective structure. Such zones include the myoid, ellipsoid, and the interdigitation zones. CONCLUSIONS: A nomenclature system for normal anatomic landmarks seen on SD-OCT outputs has been proposed and adopted by the IN*OCT Panel. The panel recommends this standardized nomenclature for use in future publications. The proposed harmonizing of terminology serves as a basis for future OCT research studies.

PURPOSE:: To determine the relationship between pseudodrusen as evidenced by the presence of subretinal drusenoid deposits and choroidal thickness using a multimodal imaging approach. METHODS:: Two sets of data were analyzed. The first set was composed of consecutive patients older than 60 years with either high myopia or pseudodrusen. Correlations were calculated between the subfoveal choroidal thickness and the presence of pseudodrusen. The second set of data was obtained from a previously published data examining 90 consecutive eyes with nonexudative age-related macular degeneration so that the relationship between pseudodrusen and subfoveal choroidal thickness could be analyzed. RESULTS:: There were 96 eyes of 53 patients in the first data set, 36 (67.9%) were female and 17 (32.1%) were male. There were 34 patients (61 eyes) in the High Myopia group and 19 patients (35 eyes) in the Primary Pseudodrusen group. The mean age of the Primary Pseudodrusen group was 83.7 years and that of the High Myopia group was 74.9 years, a difference that was significant (P < 0.001). Of the 61 eyes in the High Myopia group, only 3 (4.9%) had pseudodrusen and 0 had conventional drusen. In the Primary Pseudodrusen group, all had pseudodrusen by definition, but 28 (80%) also had conventional drusen. The mean subfoveal choroidal thickness was 181.7 mum (median, 147; interquartile range, 65-225 mum) in the Primary Pseudodrusen group and 59 mum (median, 36; interquartile range, 21-90 mum) in the myopic group. Generalized estimating equation analysis showed that eyes with pseudodrusen had thicker subfoveal choroidal thickness than eyes without, a result driven by the High Myopia group. In the second set of data, while the absolute number of eyes with pseudodrusen had a choroidal thickness between 201 mum and 250 mum, the proportion with pseudodrusen was higher in eyes with thinner choroids, with a broad peak between 50 mum and 100 mum. CONCLUSION:: Our results are not consistent with a simple cause or consequence relationship between pseudodrusen and choroidal thinning, but rather with a third yet unknown factor impacting both the pseudodrusen appearance and the choroidal thinning in susceptible populations. The reasons for the relative lack of drusen and pseudodrusen formation in high myopes need to be ascertained.

PURPOSE:: To describe the prevalence and imaging characteristics of a distinct entity of epiretinal proliferation seen predominantly in association with lamellar macular holes (LMH), termed lamellar hole-associated epiretinal proliferation (LHEP). METHODS:: Retrospective observational case review of 2,030 eyes of 1,104 patients with diagnoses including LMH, full-thickness macular hole, and epiretinal membrane (ERM) imaged with spectral domain optical coherence tomography (SD-OCT) from 2008 to 2013. Lamellar hole-associated epiretinal proliferation, defined on SD-OCT imaging as an epiretinal material of homogenous medium reflectivity, was identified and its features were qualitatively compared against conventional ERM using the SD-OCT data. RESULTS:: Lamellar hole-associated epiretinal proliferation was found in 68 of 2,030 eyes (3.3%), of which 88.2% had LMH and 11.8% had full-thickness macular hole. Lamellar hole-associated epiretinal proliferation was found in 60 of 197 eyes (30.5%) with LMH and 8 of 99 eyes (8.0%) with full-thickness macular hole. Lamellar hole-associated epiretinal proliferation was not seen in 1,734 eyes with ERM, which had no inner retinal defects detectable on SD-OCT. Lamellar hole-associated epiretinal proliferation appeared as a substantial material of homogenous medium reflectivity on the epiretinal surface that demonstrated contiguity with the middle retinal layers and conformed to the adjacent retinal anatomy. Of the eyes with LHEP and LMH, 98% had splitting of the retina in the region of Henle's fiber layer in the area immediately around the partial thickness hole, whereas 88% had visible connecting tissue from the base of the lamellar hole to the proliferating epiretinal tissue. In contrast to ERM, LHEP did not induce tractional effects such as distortion or edema of the underlying normal retinal tissue. Morphologic stability was demonstrated in 97% of eyes containing LHEP in serial eye-tracked SD-OCT images for up to 63 months of retrospective follow-up. CONCLUSION:: Spectral domain optical coherence tomography imaging showed that a subset of patients with LMH had an epiretinal proliferation with medium reflectivity and no evidence of contractile properties that was contiguous with layers of the mid-retina. This phenotype differs from conventionally described ERMs in appearance and induced changes of the underlying retina. Given these distinct anatomical relationships, the presence of LHEP could affect surgical outcomes.

PURPOSE:: To describe the spectral domain optical coherence tomography findings in eyes with chronic fibrovascular pigment epithelial detachment (PED) receiving intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. METHODS:: Retrospective observational case series of patients with chronic fibrovascular PEDs receiving serial intravitreal anti-VEGF therapy. Corresponding spectral domain optical coherence tomography scans of chronic PEDs were studied in detail over multiple visits. The internal structure within the sub-PED compartment was analyzed, characteristic features were identified, and then correlated with visual outcome. RESULTS:: Thirty-eight eyes of 34 patients with fibrovascular PEDs were included. Mean and median Snellen visual acuity was 20/50 (range, 20/20-20/400). Eyes received a mean of 28.2 intravitreal anti-VEGF injections (median, 23.0; range, 3-70) administered over a mean of 36.9 months (median, 37.5; range, 6-84). A fusiform, or spindle-shaped, complex of highly organized layered hyperreflective bands was noted within each PED. Nineteen eyes demonstrated heterogenous, dilated, irregular neovascular tissue adherent to the undersurface of the retinal pigment epithelium. Additionally, 25 eyes demonstrated a hyporeflective cavity separating the choroidal neovascularization complex from the underlying choroid. CONCLUSION:: Chronic fibrovascular PEDs receiving serial anti-VEGF therapy demonstrate a characteristic fusiform complex of highly organized, layered, hyperreflective bands, termed a "multilayered PED," which is often seen in conjunction with neovascular tissue adherent to the undersurface of the retinal pigment epithelium monolayer. On the basis of previous histopathologic correlations, these bands may represent a fibrous tissue complex with contractile properties. An associated hyporeflective space, termed a "pre-choroidal cleft," separates the fusiform complex from the underlying choroid and may be due to contraction, the exudation of fluid, or both. Many of these eyes maintain good visual acuity, presumably because the neovascular and cicatricial process is suppressed within the sub-retinal pigment epithelium space by chronic anti-VEGF therapy, thus permitting the viability of the photoreceptor population through preservation of the retinal pigment epithelium.

Central serous chorioretinopathy (CSC) is characterized by leakage of fluid from the choroid into the subretinal space and, consequently, loss of central vision. The disease is triggered by endogenous and exogenous corticosteroid imbalance and psychosocial stress and is much more prevalent in men. We studied the association of genetic variation in 44 genes from stress response and corticosteroid metabolism pathways with the CSC phenotype in two independent cohorts of 400 CSC cases and 1400 matched controls. The expression of cadherin 5 (CDH5), the major cell-cell adhesion molecule in vascular endothelium, was down-regulated by corticosteroids which may increase permeability of choroidal vasculature, leading to fluid leakage under the retina. We found a significant association of 4 common CDH5 SNPs with CSC in male patients in both cohorts. Two common intronic variants, rs7499886:A>G and rs1073584:C>T, exhibit strongly significant associations with CSC; p=0.00012; OR=1.5; 95%C.I. [1.2;1.8], and p=0.0014; OR=0.70; 95%C.I. [0.57;0.87], respectively. A common haplotype was present in 25.4% male CSC cases and in 35.8% controls (p=0.0002; OR=0.61, 95%CI [0.47-0.79]). We propose that genetically pre-determined variation in CDH5, when combined with triggering events such as corticosteroid treatment or severe hormonal imbalance, underlie a substantial proportion of CSC in the male population

PURPOSE: To subclassify pseudodrusen based on their appearance in the multimodal imaging. DESIGN: Retrospective, observational series. METHODS: The color fundus photographs and infrared scanning laser ophthalmoscope (IR-SLO) images of patients with pseudodrusen were evaluated along with spectral domain optical coherence tomography (SD-OCT) by masked readers. Distinct types of pseudodrusen could be differentiated. RESULTS: There were 140 eyes of 93 patients with a mean age of 82.4 years. Multimodal imaging analysis showed 3 subtypes of pseudodrusen. One principal type was an orderly array of whitish discrete accumulations principally located in the perifovea, termed dot pseudodrusen. They appeared as hyporeflective spots, often with a target configuration, in IR-SLO images. The second type was interconnected bands of yellowish-white material forming a reticular pattern, called ribbon pseudodrusen, which were located in the perifovea. This subtype was faintly hyporeflective in IR-SLO imaging. Dot pseudodrusen were detected more commonly with IR-SLO imaging than color photography (P=. 014) and ribbon pseudodrusen were seen more frequently in color than in IR-SLO images (P<. 001). An uncommon third type of pseudodrusen, yellow-white globules primarily located peripheral to the perifoveal region, appeared hyperreflective in IR-SLO and were called peripheral pseudodrusen. All 3 types were seen as subretinal drusenoid deposits by SD-OCT. CONCLUSION: Pseudodrusen may be classified into at least 3 categories, each with optimal methods of detection and only one that formed a reticular pattern. These findings suggest pseudodrusen could contain differing constituents and therefore, may vary in conferred risk for progression to advanced age-related macular disease.

PURPOSE: To assess the visual and anatomic outcomes of central serous chorioretinopathy (CSC) after verteporfin photodynamic therapy (PDT). DESIGN: Retrospective case series. PARTICIPANTS: Patients with CSC who underwent PDT. METHODS: Members of the Macula Society were surveyed to retrospectively collect data on PDT treatment for CSC. Patient demographic information, PDT treatment parameters, fluorescein angiographic information, optical coherence tomography (OCT) metrics, pre- and post-treatment visual acuity (VA), and adverse outcomes were collected online using standardized forms. MAIN OUTCOME MEASURES: Visual acuities over time and presence or absence of subretinal fluid (SRF). RESULTS: Data were submitted on 265 eyes of 237 patients with CSC with a mean age of 52 (standard deviation [+/- 11]) years; 61 were women (26%). Mean baseline logarithm of the minimum angle of resolution (logMAR) VA was 0.39+/-0.36 (20/50). Baseline VAs were >/=20/32 in 115 eyes (43%), 20/40 to 20/80 in 97 eyes (37%), and /=3 lines in <1%, 29%, and 48% of eyes with baseline VA >/=20/32, 20/40 to 20/80, and 0.01). Complications were rare: Retinal pigment epithelial atrophy was seen in 4% of patients, and acute severe visual decrease was seen in 1.5% of patients. CONCLUSIONS: Photodynamic therapy was associated with improved VA and resolution of SRF. Adverse side effects were rare.