Faculty Bibliography

PURPOSE: To define the phenotypic characteristics of the bullous variant of central serous chorioretinopathy (CSC) using multimethod imaging. DESIGN: Retrospective, observational case series. PARTICIPANTS: Twenty-one eyes of 14 patients with bullous retinal detachment resulting from CSC (bullous CSC group) and 122 eyes of 84 patients with chronic CSC without bullous retinal detachment (nonbullous CSC group). METHODS: We performed a retrospective review of clinical and multimethod imaging data of patients who sought treatment from the authors with bullous retinal detachment resulting from CSC between January 2010 and November 2015. Multimethod imaging comprised color photography, fluorescein angiography, fundus autofluorescence, and high-resolution optical coherence tomography. Consecutive cases of chronic CSC without bullous retinal detachment, seen during the same period, comprised a comparative group. MAIN OUTCOME MEASURES: Qualitative and quantitative characteristics of the choroid, retinal pigment epithelium, and retina were compared between the 2 groups. RESULTS: Mean age of the bullous CSC group was 53.8 years. There was no difference in age, visual acuity, corticosteroid use, or the proportion of white patients and men between the 2 groups (all P > 0.132). Peripheral nonperfusion occurred only in eyes with bullous retinal detachment (38% of cases). Retinal pigment epithelial tears were seen in 95% of eyes in the bullous group and none of the eyes in the nonbullous CSC group. The bullous CSC group demonstrated a greater number of pigment epithelial detachments (PEDs) and more eyes demonstrated PEDs with internal hyperreflectivity (both P < 0.016). Mean subfoveal choroidal thickness in the bullous CSC group (463.1+/-83.1 mum) was not different compared with that of the nonbullous CSC group (400.6+/-100.6 mum; P = 0.993). More eyes in the bullous CSC group demonstrated hyperreflectivity around large choroidal vessels and at the level of the choriocapillaris on OCT (P < 0.001). Retinal folds and subretinal fibrin were identified in a greater proportion of eyes in the bullous CSC group (both P < 0.001). CONCLUSIONS: Bullous retinal detachment is a rare manifestation of chronic CSC and is characterized by a unique constellation of phenotypic and multimethod imaging features.

PURPOSE: To describe the clinical and imaging findings in 3 patients with maculopathy secondary to handheld laser exposure. DESIGN: Retrospective, observational case series. METHODS: We evaluated the multimodal imaging including fundus autofluorescence and spectral-domain optical coherence tomography (OCT) for 3 patients with histories of exposure to handheld lasers. RESULTS: An 18-year-old woman with a history of repetitive self-inflicted handheld laser exposure was found to have bilateral outer retinal streaks in the macula and the superior peripheral retina on both ophthalmoscopy and multimodal imaging. Initial spectral-domain OCT revealed vertical hyper-reflective bands at the level of the outer retina corresponding to the streaks. An 11-year-old boy who played with a green laser developed a yellow foveal lesion and outer retinal streaks in the superior macula. Spectral-domain OCT showed vertical hyper-reflective bands in the outer retina corresponding to the streaks. A 14-year-old boy developed bilateral focal foveal lesions and ellipsoid loss on spectral-domain OCT following peer-inflicted laser injury. CONCLUSIONS: In a series of 3 patients, outer retinal streaks were associated with self-inflicted handheld laser injury. In contrast, accidental and peer-inflicted laser injuries were found to result in focal foveal lesions.

This study investigated whether the presence of vitreomacular interface abnormalities (VMIAs) affects the improvement in visual acuity and edema of patients with diabetic macular edema (DME) who received three anti-vascular endothelial growth factor (VEGF) injections. Fifteen eyes of 11 patients with clinically significant macular edema were retrospectively divided into either the control group (only DME) or the experimental group (DME and VMIA) based on optical coherence tomography images. We defined VMIA patterns as epiretinal membrane and/or anomalous vitreomacular adhesion. Changes in central macular thickness (CMT), total macular volume (TMV), and best-corrected visual acuity (BCVA) from the baseline to post third injection were compared between the two groups. After the third injection, the decreases in CMT and TMV were not statistically different between the two groups. The improvement in BCVA was larger in the control group (0.1742 +/- 0.0508 logMAR) than in the experimental group (0.0766 +/- 0.0562 logMAR; p < 0.01). Our study showed that after the third anti-VEGF injection, the BCVA of patients with both DME and VMIAs improved significantly less than that of patients with only DME. Our results suggest that VMIAs may play a crucial role in reducing the therapeutic effects of anti-VEGF agents.

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

IMPORTANCE New funduscopic findings in patients with enhanced S-cone syndrome (ESCS) may help clinicians in diagnosing this rare autosomal recessive retinal dystrophy. OBJECTIVE To expand the clinical spectrum of ESCS due to mutations in the NR2E3 gene. DESIGN Retrospective, noncomparative case series of 31 patients examined between 1983 and 2012. SETTING Academic and private ophthalmology practices specialized in retinal dystrophies. PARTICIPANTS A cohort of patients diagnosed with ESCS and harboring known NR2E3 mutations. INTERVENTION Patients had ophthalmic examinations including visual function testing that led to the original diagnosis. MAIN OUTCOMES AND MEASURES New fundus features captured with imaging modalities. RESULTS New clinical observations in ESCS include (1) torpedo-like, deep atrophic lesions with a small hyperpigmented rim, variably sized and predominantly located along the arcades; (2) circumferential fibrotic scars in the posterior pole with a spared center and large fibrotic scars around the optic nerve head; and (3) yellow dots in areas of relatively normal-appearing retina. CONCLUSIONS AND RELEVANCE Enhanced S-cone syndrome has more pleiotropy than previously appreciated. While the nummular type of pigmentation at the level of the retinal pigment epithelium and cystoid or schisis-like maculopathy with typical functional findings remain classic hallmarks of the disease, changes such as circumferential fibrosis of the macula or peripapillary area and "torpedo-like" lesions along the vascular arcades may also direct the clinical diagnosis and focus on screening the NR2E3 gene for a molecular diagnosis.

IMPORTANCE: With the advent of more sophisticated imaging systems, such as spectral domain optical coherence tomography (SD-OCT), disruption of the inner segment/outer segment (IS/OS) band, and thinning of the outer nuclear layer (ONL) have been identified in association with acute macular neuroretinopathy (AMN). OBJECTIVES: To characterize a new SD-OCT presentation of AMN as a paracentral acute middle maculopathy and to describe multimodal imaging findings that implicate an underlying pathogenesis related to retinal capillary ischemia. DESIGN, SETTING, AND PARTICIPANTS: Retrospective observational case series (January 1, 2012, to January 1, 2013) reviewing clinical and imaging data from 9 patients (11 eyes) with AMN at 6 tertiary referral centers. Lesions were classified as type 1 or 2 in relation to the SD-OCT location of the lesion above (type 1) or below (type 2) the outer plexiform layer (OPL) at 6 tertiary referral centers. RESULTS: Of the 9 patients, 5 were female and 4 were male (mean age, 47.6 years; range, 21-65 years). All patients presented with an acute paracentral scotoma and demonstrated a classic dark gray paracentral lesion with near-infrared imaging. Visual acuity ranged from 20/15 to 20/30. Six eyes (5 patients) had type 1 SD-OCT lesions, also referred to as paracentral acute middle maculopathy, and 5 eyes (4 patients) had type 2 SD-OCT lesions. Although type 1 lesions lead to inner nuclear layer (INL) thinning, type 2 lesions resulted in ONL thinning. Type 2 lesions were always associated with significant outer macular defects, including disruption of the inner segment/outer segment and outer segment/retinal pigment epithelium bands, whereas type 1 lesions spared the outer macula. CONCLUSIONS AND RELEVANCE: Paracentral acute middle maculopathy may represent a novel variant of AMN that affects the middle layers of the macula above the OPL as diagnosed with SD-OCT imaging. Two types of AMN lesions may be seen with SD-OCT occurring above and below the OPL. Type 1 refers to hyperreflective bands in the OPL/INL region with subsequent INL thinning. Type 2 is hyperreflective bands in the OPL/ONL region with subsequent ONL thinning. Type 2 lesions may be associated with concomitant defects of the inner segment/outer segment layer. We propose that each of these lesions may be explained by occlusion of either the superficial capillary plexus (type 1) or deep capillary plexus (type 2) located in the innermost and outermost portion of the INL, respectively, immediately adjacent to each corresponding lesion type.

PURPOSE: To report one year outcomes of focal Navigated Retina Laser Therapy (NAVILAS) for diabetic macular edema (DME). METHODS: Retrospective cohort series of 7 diabetic patients treated with NAVILAS focal laser. Statistical analysis included descriptive and continuous variables (Best-corrected logMAR Visual Acuity and time-domain optical coherence tomography (OCT) parameters) which were compared using a non-parametric procedure, the Friedman tests for repeated measures. A p-value of less than 0.05 was considered to denote statistical significance. RESULTS: diabetic patients (4 male; 3 female) with an average age of 60.8 years (range 48-85 years) were included. All treated eyes were phakic; patients had an average hemoglobin A1C of 9.1 (range 7.8-11.7) at baseline and 8.0 (range 7.4-8.4) at 12 months. Six of the 7 patients had intravitreal bevacizumab injections prior to focal laser treatment with 1 patient having had more than 1 prior injection (total 3). At 12 months, median logMAR improved from 0.695 (+/- interquartile range 0.574) to 0.477 (+/- 0.573, p <0.001). OCT median central foveal thickness decreased from 248 (+/- 112) to 220 microm (+/- 41, p <0.001); total macular volume decreased from 7.84 (+/- 0.8) to 7.44 mm3 (+/- 0.7, p = 0.117); and largest macular subfield thickness decreased from 354 (+/- 116) to 289 microm (+/- 42, p <0.001). All patients were treated without complications. CONCLUSIONS: Focal NAVILAS showed to be safe and effective in treating DME with improvement in visual acuity and macular edema on OCT over 12 months in this case series. In clinical practice, combined treatment with focal laser including NAVILAS and anti-vascular endothelial growth factor may provide long-term improvement in DME.

Purpose To report novel multimodal imaging findings in acute macular neuroretinopathy (AMN) which implicate an underlying ischemic pathogenesis. A simple classification system is proposed to reflect the location of SD-OCT lesions in AMN that affect the outer plexiform layer (OPL)/inner nuclear layer (INL) junction of the inner macula (Type 1) versus the OPL/outer nuclear layer (ONL) region of the outer macula (Type 2). Methods Retrospective observational case series reviewing clinical and imaging data from 8 patients (10 eyes) with AMN. All patients demonstrated classic parafoveal, dark grey, wedge-like lesions with NIR reflectance and characteristic abnormalities with SD-OCT imaging that were classified as Type 1 or 2 in relation to the location of the lesion above (Type 1) or below (Type 2) the OPL. Results Of the 8 patients, 5 were female and 3 were male, averaging 46.8 years in age (range, 21-65). Seven of the individuals were Caucasian, and the other was African American. The retinal lesions were unilateral in all but 2 cases. Visual acuity (VA) in the affected eyes at the time of presentation ranged from 20/15 to 20/30. After an average follow-up of 9.5 weeks (range, 3-30), VA ranged from 20/20 to 20/30. Five eyes (4 patients) had Type 1 lesions and 5 eyes (4 patients) had Type 2 lesions. While Type 1 lesions lead to thinning of the INL, Type 2 lesions resulted in thinning of the ONL. Type 2 lesions were always associated with significant outer macular defects including attenuation of the inner segment/outer segment (IS/OS) and outer segment/retinal pigment epithelium (OS/RPE) bands, whereas Type 1 lesions failed to disrupt the integrity of the IS/OS junction. Conclusions The diagnosis of AMN has vastly improved with the integration of multimodal imaging. Two types of AMN lesions may be seen with SD-OCT occurring above and below the OPL: Type 1. Hyperreflective bands in the OPL/INL region with subsequent INL thinning, and Type 2. Hyperreflective bands in the OPL/ONL region with subsequent ONL thinning. Type 2 lesions may be associated with concomitant defects of the IS/OS band. We propose that each of these lesions may be explained by occlusion of the superficial capillary plexus (SCP) (Type 1) or deep capillary plexus (DCP) (Type 2) located in the innermost and outermost portion of the INL respectively immediately adjacent to each corresponding lesion type