Faculty Bibliography

PURPOSE/OBJECTIVE:To evaluate the long-term visual outcomes and causes of vision loss in chronic central serous chorioretinopathy (CSC). DESIGN/METHODS:Retrospective, longitudinal study SUBJECTS: One-hundred and thirty-three subjects (217 eyes) with chronic CSC. METHODS:A retrospective review of clinical and multimodal imaging data of patients with chronic CSC managed by 3 of the authors between May 1977 and March 2018. Multimodal imaging comprised color photography, fluorescein angiography, indocyanine green angiography, fundus autofluorescence (FAF) and optical coherence tomography (OCT). MAIN OUTCOME MEASURES/METHODS:Best corrected visual acuity (BCVA) at the final visit; change in BCVA between first visit and 1, 5 and 10-year follow-up visits, and causes of vision loss at final visit. RESULTS:Data from 6,228 individual clinic visits were analyzed. Mean age of patients at the first visit was 60.7 years and mean period of follow-up from first to last visit was 11.3 years. The cohort included 101 males (75.9%). At the final visit, 106 patients (79.7%) maintained driving-standard vision with BCVA of 20/40 or better in at least one eye and 17 patients (12.8%) were legally blind with BCVA of 20/200 or worse in both eyes. Mean BCVA at first visit was not significantly different from mean BCVA at 1 or 5-year follow-up visits (both p≥0.65) but was significantly better than the mean BCVA at the 10-year follow-up visit (p=0.04). Seventy-nine percent of eyes with 20/40 or better vision at the first visit maintained the same level of vision at the 10-year follow-up visit. Ninety-two percent of eyes with 20/200 or worse vision at the first visit maintained the same level of vision at the 10-year follow-up visit. Cystoid macular degeneration, choroidal neovascularization, outer retinal disruption on OCT and FAF changes were associated with poorer vision at final visit (all p≤0.001). Multivariable analysis revealed that greater age at first visit was associated with greater BCVA change at the 10-year follow-up visit (p=0.001). CONCLUSION/CONCLUSIONS:Chronic CSC can be a sight-threatening disease leading to legal blindness. Age at presentation and outer retinal changes on multimodal imaging were associated with long-term BCVA changes and may be predictors of long-term visual outcomes.

PURPOSE/OBJECTIVE:To investigate the macular changes over time in eyes containing subretinal drusenoid deposits (also known as pseudodrusen) with no drusen >63 µm. METHODS:A consecutive series of patients were examined with color fundus photography, optical coherence tomography, and autofluorescence imaging with fluorescein angiography used as necessary. Exclusionary criteria included macular neovascularization, history of retinal surgery, pseudoxanthoma elasticum, and drusen >63 µm. RESULTS:There were 85 eyes of 54 patients. The mean age at baseline was 83.6 (±7.8) years, and there were 17 men. The mean follow-up was 5.0 (±2.9) years. At initial optical coherence tomography examination, 12 eyes had extrafoveal atrophy and 17 eyes had vitelliform deposits, which were yellowish white subretinal collections that showed intense hyperautofluorescence. During follow-up, 11 eyes lost vitelliform material. After the disappearance of small deposits, focal hyperpigmentation remained. Loss of larger deposits was associated with noteworthy sequela; six developed subfoveal atrophy and one macular neovascularization close to regressing vitelliform material. Subfoveal geographic atrophy developed in four other eyes without vitelliform material by extension from areas of extrafoveal atrophy. Macular neovascularization developed in seven eyes over follow-up. The CFH Y402H and ARMS2 A69S allele frequencies were 57% and 48.9%, respectively, which is similar to a group of age-related macular degeneration controls. One patient had a novel PRPH2 mutation, but did not have a vitelliform deposit; the remainder had a normal PRPH2 and BEST1 coding sequences. CONCLUSION/CONCLUSIONS:Eyes with subretinal drusenoid deposits and no drusen >63 mm have significant risk for the development of both neovascularization and geographic atrophy, the fundamental components of late age-related macular degeneration. An intermediate step in some eyes was the development of a vitelliform deposit, an entity not traditionally associated with age-related macular degeneration, but in these patients, the material seemed to be an important component of the disease pathophysiology. This vitelliform deposit was not associated with genetic markers for pattern dystrophy or Best disease.

A distinction between conventional drusen and pseudodrusen was first made in 1990, and more recently knowledge of pseudodrusen, more accurately called subretinal drusenoid deposits (SDD), has expanded. Pseudodrusen have a bluish-white appearance by biomicroscopy and color fundus photography. Using optical coherence tomography, pseudodrusen were found to be accumulations of material internal to the retinal pigment epithelium (RPE) that could extend internally through the ellipsoid zone. These deposits are more commonly seen in older eyes with thinner choroids. Histologic evaluation of these deposits revealed aggregations of material in the subretinal space between photoreceptors and RPE. SDD contain some proteins in common with soft drusen, but differ in lipid composition. Many studies reported that SDD are strong independent risk factors for late age-related macular degeneration (AMD). Geographic atrophy and Type 3 neovascularization are particularly associated with SDD. Unlike conventional drusen, eyes with SDD show slowed dark adaptation and poor contrast sensitivity. Eyes with regression of SDD develop outer retinal atrophy, which is a newly recognized form of late AMD. Advances in imaging technology have enabled many insights into this condition, including associated photoreceptor, RPE, and underlying choroidal changes.

PURPOSE/OBJECTIVE:To report a unilateral case of what is named bilateral diffuse uveal melanocytic proliferation and consider the consequences of this finding. METHODS:The ocular findings were investigated with multimodal imaging to include color fundus photography, fluorescein angiography, autofluorescence imaging, and enhanced depth imaging optical coherence tomography. RESULTS:A 66-year-old woman had a history of breast cancer 23 years previously that was treated and the patient was free of disease since. She developed a recent decrease in visual acuity in her left eye prompting referral. She was seen to have an alteration in the pigmentation of the posterior pole of the left eye with dispersed red placoid spots. Autofluorescence imaging showed nummular areas of absent autofluorescence signal, which corresponded to areas of hyperfluorescence during fluorescein angiography. The placoid spots were hyperautofluorescent and hypofluorescent in autofluorescence and fluorescein angiography, respectively. She had diffuse thickening and infiltration of the choroid in the left eye. Because of the ocular findings, the patient underwent a systemic evaluation and was found to have widely metastatic disease with an unknown primary cancer. No progression of disease was seen in the left eye over a 6-month follow-up, and the right eye never showed any abnormality, except for a modest cataract, by any means of examination. CONCLUSION/CONCLUSIONS:Bilateral uveal melanocytic proliferation has been attributed to a paraneoplastic process, allegedly from a factor in the IgG fraction of the serum. However, unilateral involvement suggests that there are other factors involved in disease manifestation.

PURPOSE/OBJECTIVE:To investigate the deep retinal vascular changes potentially present in macular telangiectasis Type 2 (MacTel 2) with projection resolved optical coherence tomography angiography including volume rendering. METHODS:Retrospective consecutive evaluation of patients with MacTel 2 in a community-based retinal referral practice with a comprehensive ophthalmologic examination to include optical coherence tomography and projection-resolved optical coherence tomography angiography with volume rendering. Main outcome measures were the characterization of vessel presence and anatomical arrangement in the outer retina. RESULTS:There were 26 eyes of 13 patients with a mean age of 64.9 (±11.3) years, and 6 were men. The mean visual acuity was logMAR 0.4 (Snellen equivalent 20/50). No eye had signs of choroidal neovascularization or exudation. Focal hyperpigmentation was seen in 13 (50%) and right-angle veins in 17 (65%) eyes. Retinal-choroidal anastomoses were seen in 17 (65%) eyes. These anastomoses typically occurred in multiple clusters of small vessels. The presence of anastomoses was associated with pigment (P < 0.001), although the anastomoses did not necessarily colocalize with the pigment, and right-angle veins (P < 0.001), which were found in every eye with a retinal-choroidal anastomosis. CONCLUSION/CONCLUSIONS:Retinal-choroidal anastomoses were commonly observed in eyes with MacTel 2 using projection-resolved optical coherence tomography angiography. One animal model for MacTel 2 uses very low-density lipoprotein receptor mutant mice and shows multiple retinal-choroidal anastomoses in the disease pathogenesis as well. These findings suggest MacTel 2 is more than just a neurodegenerative disease with secondary vascular abnormalities, as the choroid may be involved in the disease process.

Previous models of disease in age-related macular degeneration (AMD) were incomplete in that they did not encompass subretinal drusenoid deposits (pseudodrusen), subtypes of neovascularization, and polypoidal choroidal vasculopathy. In addition, Type 3 neovascularization starts in the retina and may not necessarily involve the choroid. As such, the term choroidal neovascularization is not appropriate for these eyes. The new aspects in the AMD construct are to include specific lipoprotein extracellular accumulations, namely drusen and subretinal drusenoid deposits, as early AMD. The deposition of specific types of deposit seems to be highly correlated with choroidal thickness and topographical location in the macula. Late AMD includes macular neovascularization or atrophy. The particular type of extracellular deposit is predictive of the future course of the patient. For example, eyes with subretinal drusenoid deposits have a propensity to develop outer retinal atrophy, complete outer retinal and retinal pigment epithelial atrophy, or Type 3 neovascularization as specific forms of late AMD. Given Type 3 neovascularization may never involve the choroid, the term macular neovascularization is suggested for the entire spectrum of neovascular disease in AMD. In contrast to older classification systems, the proposed system encompasses the relevant presentations of disease and more precisely predicts the future course of the patient. In doing so, the concept was developed that there may be genetic risk alleles, which are not necessarily the same alleles that influence disease expression.

Optical coherence tomography (OCT) was one of the biggest advances in ophthalmic imaging. Building on that platform, OCT angiography (OCTA) provides depth resolved images of blood flow in the retina and choroid with levels of detail far exceeding that obtained with older forms of imaging. This new modality is challenging because of the need for new equipment and processing techniques, current limitations of imaging capability, and rapid advancements in both imaging and in our understanding of the imaging and applicable pathophysiology of the retina and choroid. These factors lead to a steep learning curve, even for those with a working understanding dye-based ocular angiography. All for a method of imaging that is a little more than 10 years old. This review begins with a historical account of the development of OCTA, and the methods used in OCTA, including signal processing, image generation, and display techniques. This forms the basis to understand what OCTA images show as well as how image artifacts arise. The anatomy and imaging of specific vascular layers of the eye are reviewed. The integration of OCTA in multimodal imaging in the evaluation of retinal vascular occlusive diseases, diabetic retinopathy, uveitis, inherited diseases, age-related macular degeneration, and disorders of the optic nerve is presented. OCTA is an exciting, disruptive technology. Its use is rapidly expanding in clinical practice as well as for research into the pathophysiology of diseases of the posterior pole.

PURPOSE/OBJECTIVE:To investigate the relationship between subfoveal choroidal thickness and disease manifestation in a series of eyes with nonexudative age-related macular degeneration (AMD). METHODS:Retrospective study of eyes with nonexudative AMD. The extracellular deposits present, drusen and subretinal drusenoid deposits (SDD, pseudodrusen) along with a newly recognized form of drusen, pachydrusen, were graded and compared with choroidal thickness as determined by optical coherence tomography. Demographic and imaging information was evaluated with descriptive statistics and generalized estimating equations. RESULTS:There were 94 eyes of 71 patients, who had a mean age of 78.1 years. Soft drusen alone were found in 45 eyes (47.9%) and subretinal drusenoid deposit with or without drusen in 38 (40.4%). Pachydrusen, which were typically larger than 125 μm, often had an irregular outer contour, showed a scattered distribution over the posterior pole and occurred in isolation or in groups of only a few drusen were found in 11 (11.7%). The mean subfoveal choroidal thickness in the soft drusen group was 227.9 μm, in the subretinal drusenoid deposit group 167.3 μm, and in the pachydrusen group 419 μm. The differences between the groups were highly significant. CONCLUSION/CONCLUSIONS:Extracellular deposits, subretinal drusenoid deposits and drusen, which are on either side of the retinal pigment epithelium, respectively, are common in nonexudative AMD. A new form of drusen presentation could be differentiated from typical soft drusen and was associated with thicker choroids. Disease manifestation in nonexudative AMD seems to be associated with choroidal thickness. Each of these has potential to lead to specific forms of late AMD.