Faculty Bibliography

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.

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.

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.

PURPOSE/OBJECTIVE:To develop consensus terminology and criteria for defining atrophy based on OCT findings in the setting of age-related macular degeneration (AMD). DESIGN/METHODS:Consensus meeting. PARTICIPANTS/METHODS:Panel of retina specialists, image reading center experts, retinal histologists, and optics engineers. METHODS:As part of the Classification of Atrophy Meetings (CAM) program, an international group of experts surveyed the existing literature, performed a masked analysis of longitudinal multimodal imaging for a series of eyes with AMD, and reviewed the results of this analysis to define areas of agreement and disagreement. Through consensus discussions at 3 meetings over 12 months, a classification system based on OCT was proposed for atrophy secondary to AMD. Specific criteria were defined to establish the presence of atrophy. MAIN OUTCOME MEASURES/METHODS:A consensus classification system for atrophy and OCT-based criteria to identify atrophy. RESULTS:OCT was proposed as the reference standard or base imaging method to diagnose and stage atrophy. Other methods, including fundus autofluorescence, near-infrared reflectance, and color imaging, provided complementary and confirmatory information. Recognizing that photoreceptor atrophy can occur without retinal pigment epithelium (RPE) atrophy and that atrophy can undergo an evolution of different stages, 4 terms and histologic candidates were proposed: complete RPE and outer retinal atrophy (cRORA), incomplete RPE and outer retinal atrophy, complete outer retinal atrophy, and incomplete outer retinal atrophy. Specific OCT criteria to diagnose cRORA were proposed: (1) a region of hypertransmission of at least 250 μm in diameter, (2) a zone of attenuation or disruption of the RPE of at least 250 μm in diameter, (3) evidence of overlying photoreceptor degeneration, and (4) absence of scrolled RPE or other signs of an RPE tear. CONCLUSIONS:A classification system and criteria for OCT-defined atrophy in the setting of AMD has been proposed based on an international consensus. This classification is a more complete representation of changes that occur in AMD than can be detected using color fundus photography alone. Longitudinal information is required to validate the implied risk of vision loss associated with these terms. This system will enable such future studies to be undertaken using consistent definitions.

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 describe cases presenting with features of idiopathic macular telangiectasia (MacTel) Type 2 and central serous chorioretinopathy (CSC). METHODS:Databases from four tertiary retina centers were searched for cases copresenting CSC and MacTel Type 2. RESULTS:Five cases were identified (4 men, 1 woman; mean age: 67.2 years). Four patients were referred for chronic or nonresolving CSC, and the diagnosis of MacTel Type 2 was made based on multimodal imaging findings. One patient had advanced MacTel Type 2, and developed acute CSC. Regarding the MacTel Type 2 findings, all subjects presented perifoveal telangiectasia on fluorescein angiography, and four subjects showed intraretinal cavitations typical of MacTel Type 2 on optical coherence tomography, in one or both eyes. Regarding the CSC findings, fluorescein angiography identified focal or extended retinal pigment epithelium alteration in all eyes, and an active leakage in two eyes. Indocyanine green angiography showed choroidal vascular hyperpermeability in four subjects. On optical coherence tomography, pigment epithelial detachments were detected in five eyes (four subjects), and foveal detachments were present in five eyes (three subjects), which spontaneously resolved (two eyes), responded to photodynamic therapy (two eyes), or persisted (one eye). Mean choroidal thickness was 402 ± 99 μm. CONCLUSION/CONCLUSIONS:The codiagnosis of CSC and MacTel Type 2 should be considered in atypical presentations associating features from both disorders.

PURPOSE/OBJECTIVE:To develop a mathematical model of local blood flow in the choriocapillaris using an Ising model. METHODS:A JavaScript Ising model was used to create images that emulated the development of signal voids as would be seen in optical coherence tomography angiography of the choriocapillaris. The model was produced by holding the temperature near criticality and varying the field strength. Individual frames were evaluated, and a movie video was created to show the hypothetical development of flow-related signal voids over a lifetime. RESULTS:Much the same as actual choriocapillaris images in humans, the model of flow-related signal voids followed a power-law distribution. The slope and intercept both decreased with age, as is seen in human subjects. CONCLUSION/CONCLUSIONS:This model is a working hypothesis, and as such can help predict system characteristics, evaluate conclusions drawn from studies, suggest new research questions, and provide a way of obtaining an estimate of behavior in which experimental data are not yet available. It may be possible to understand choriocapillaris blood flow in health and disease states by determining by observing deviations from an expected model.

PURPOSE/OBJECTIVE:To examine the alterations in retinal vascular morphology over an extended follow-up in eyes with macular telangiectasis Type 2 (MacTel2). METHODS:Eyes with high-quality digital photographs were evaluated. The geometric distortion in baseline images required to emulate the follow-up images was determined and vectors were made that represented the direction and magnitude of changes, to create a warp field. Optical coherence tomography and optical coherence tomography angiography evaluation of the retina was performed. RESULTS:There were 7 eyes of 4 patients, who had a mean age of 70.25 years, which were followed for a mean of 8.8 years. The eyes showed increasing grayish opacification in the temporal macula with straightening and displacement of the macular vessels, even those in the nasal macula. The warp field vectors pointed to the temporal juxtafoveal macula. There was never any cavitation at the epicenter of the retinal distortion in any patient, although cavitations were found around this area. Optical coherence tomography imaging showed a circumscribed region of hyperreflectivity in the temporal macula. Optical coherence tomography angiography showed a deep angular condensed network of vessels within the hyperreflective region. One eye showed marked atrophic changes including full-thickness macular hole formation, but no increase in graying of the retina, loss of retinal laminations, pigmentary infiltration, or alteration in the retinal vessels. CONCLUSION/CONCLUSIONS:Tissue contraction with retinal vascular displacement and contortion seem to be integral aspects of disease manifestation in MacTel2. The induced vascular changes may lead to secondary effects that increase morbidity in this disease.

PURPOSE/OBJECTIVE:To investigate the natural history of dot subretinal drusenoid deposits (SDD) in age-related macular degeneration, using high-resolution adaptive optics scanning laser ophthalmoscopy. METHODS:Six eyes of four patients with intermediate age-related macular degeneration were studied at baseline and 1 year later. Individual dot SDD within the central 30° retina were examined with adaptive optics scanning laser ophthalmoscopy and optical coherence tomography. RESULTS:A total of 269 solitary SDD were identified at baseline. Over 12.25 ± 1.18 months, all 35 Stage 1 SDD progressed to advanced stages. Eighteen (60%) Stage 2 lesions progressed to Stage 3 and 12 (40%) remained at Stage 2. Of 204 Stage 3 SDD, 12 (6.4%) disappeared and the rest remained. Twelve new SDD were identified, including 6 (50%) at Stage 1, 2 (16.7%) at Stage 2, and 4 (33.3%) at Stage 3. The mean percentage of the retina affected by dot SDD, measured by the adaptive optics scanning laser ophthalmoscopy, increased in 5/6 eyes (from 2.31% to 5.08% in the most changed eye) and decreased slightly in 1/6 eye (from 10.67% to 10.54%). Dynamism, the absolute value of the areas affected by new and regressed lesions, ranged from 0.7% to 9.3%. CONCLUSION/CONCLUSIONS:Adaptive optics scanning laser ophthalmoscopy reveals that dot SDD, like drusen, are dynamic.

PURPOSE/OBJECTIVE:To assess anatomic and visual outcomes of ocriplasmin use for symptomatic vitreomacular adhesion (VMA). DESIGN/METHODS:Retrospective chart review. METHODS:Macula Society members were surveyed online to collect data on ocriplasmin for symptomatic VMA. Clinical and optical coherence tomography data were collected using standardized data entry forms. RESULTS:There were 208 patients (208 eyes) with symptomatic VMA followed at least 3 weeks after receiving ocriplasmin. At baseline, VMA was focal (<1500 μm) in 179 eyes (86%), broad in 9 eyes (4%), and not reported in 20 eyes (10%). A full-thickness macular hole (MH) was present in 75 eyes (36%); size was <400 μm in 62 eyes (82%). Baseline mean visual acuity was approximately 20/63. Of the 204 eyes with ≥12 weeks follow-up, pars plana vitrectomy (PPVx) was performed in 12 (6%) by 4 weeks, 31 (15%) by 12 weeks, and 64 (31%) by the last visit. VMA had resolved by 12 weeks with ocriplasmin alone in 83 of 191 eyes (43%) by week 12 and in 148 of 200 eyes (74%) by the last visit, including eyes undergoing PPVx. Among eyes with a baseline MH, closure was achieved with ocriplasmin alone in 10 of 65 (15%) by 1 week, 26 of 74 (35%) by 4 weeks, and 30 of 75 (40%) at the last visit. Mean change in visual acuity at the last visit compared with baseline was -0.06±0.40 logarithm of the minimum angle of resolution (logMAR) (modest vision improvement) (P = 0.03). At the last visit, visual acuity improved by ≥2 lines in 69 eyes (35%) and by ≥3 lines in 54 eyes (27%). Visual acuity decreased ≥2 lines in 35 eyes (18%) and by 3 lines in 27 eyes (14%) at the final visit. Complications included photopsias (15%), dimness of vision (14%), decreased color vision (10%), MH development (5%), macular retinal pigment epithelium atrophy (2.7%), retinal detachment (1.9%), and retinal tear (1.4%). No endophthalmitis cases were reported. CONCLUSIONS:Physician-reported outcomes on ocriplasmin use confirmed VMA release in 45% and closure of MH in 40% of eyes without PPVx. Visual acuity decreased in approximately 20% of eyes. Adverse events were not infrequent and suggest caution when considering ocriplasmin use.