Immunomodulatory Treatment Versus Systemic Steroids in Inflammatory Choroidal Neovascularization Secondary to Idiopathic Multifocal Choroiditis.

PURPOSE: To evaluate the influence of immunomodulatory therapy (IMT) on visual and treatment outcomes of inflammatory choroidal neovascularization (iCNV) in patients affected by multifocal choroiditis (MFC), and to compare them to patients treated with steroids as needed. DESIGN: Multicenter retrospective matched cohort study. METHODS: Patients affected by MFC with iCNV were divided into a IMT group and a "steroids as needed" group and matched according to the time between diagnosis and beginning of systemic treatment. Visual acuity (VA), number of anti-vascular endothelial growth factor (VEGF) intravitreal injections, and number of iCNV reactivations during 2 years of follow-up after treatment initiation were compared between the 2 groups. RESULTS: A total of 66 eyes of 58 patients were included, equally divided into the 2 groups. Patients in the IMT group had a lower relative risk (RR) of iCNV reactivation (0.64, P = .04) and of anti-VEGF intravitreal injection retreatment (0.59, P = .02). Relapses of MFC-related inflammation were independently associated with a higher RRs of iCNV reactivation (1.22, P = .003). Final VA was higher in the IMT compared to the steroids as needed group (mean [SD], 69.1 [15.1] vs 77.1 [8.9] letters, P = .01), and IMT was associated with greater VA gains over time (+2.5 letters per year, P = .04). CONCLUSIONS: IMT was associated with better visual and treatment outcomes in MFC complicated by iCNV compared to steroids as needed. The better outcomes of the IMT group and the association between MFC-related inflammation and iCNV reactivations highlight the need for tighter control of inflammation to prevent iCNV relapses and visual loss.

Utility of Anterior Segment OCT in the Management of Uveitic Cataract Surgery: A Fibrinoid Syndrome Case Treated with rtPA.

PURPOSE: To highlight the importance of swept-source anterior segment optical coherence tomography (SS-ASOCT) in the peri-surgical management of cataract in uveitis. To describe a case of fibrinoid syndrome in uveitis treated with recombinant tissue plasminogen activator (rtPA). METHODS: SS-ASOCT was performed at each follow-up before and after cataract surgery to assess anterior chamber inflammation and assist the clinical management of the patient. RESULTS: A patient with idiopathic autoimmune uveitis was scheduled for cataract surgery. SS-ASOCT allowed to correctly plan the surgery timing. The patient developed a severe fibrinoid syndrome. Postsurgical SS-ASOCT allowed to distinguish between anterior chamber cells and fibrin thus guiding the timing for rtPA intracameral injection. Visual acuity improved from 20/400 the day after the surgery to 20/40. CONCLUSION: SS-ASOCT allowed a precise assessment of the inflammatory components (cellular vs fibrinoid) after cataract surgery. Intracameral rtPA was safe and effective in the treatment fibrinoid syndrome in uveitis.

Correlation Between Retinal Vessel Diameters and Uveitis Activity.

Purpose: To assess retinal vein and artery diameters during active and inactive intraocular inflammation in eyes with uveitis. Methods: Color fundus photographs and clinical data of eyes with uveitis collected during two visits (active disease [i.e., T0] and inactive stage [i.e., T1]) were reviewed. The images were semi-automatically analyzed to obtain the central retina vein equivalent (CRVE) and central retina artery equivalent (CRAE). Changes of CRVE and CRAE from T0 to T1 were calculated, and their possible correlation with clinical data, including age, gender, ethnicity, uveitis etiology, and visual acuity, were investigated. Results: Eighty-nine eyes were enrolled in the study. Both CRVE and CRAE reduced from T0 to T1 (P < 0.0001 and P = 0.01, respectively), with active inflammation being able to influence the CRVE and CRAE (P < 0.0001 and P = 0.0004, respectively) after accounting for all other variables. The degree of venular (∆V) and arteriolar (∆A) dilation was influenced only by time (P = 0.03 and P = 0.04, respectively). Best-corrected visual acuity was influenced by time and ethnicity (P = 0.003 and P = 0.0006). Conclusions: CRVE and CRAE are increased in eyes with active intraocular inflammation regardless of the type of uveitis, and they decrease when the inflammation wears off.

NATURAL COURSE AND CLASSIFICATION OF EXTENSIVE MACULAR ATROPHY WITH PSEUDODRUSEN-LIKE APPEARANCE.

PURPOSE: To describe the imaging characteristics and topographic expansion of retinal pigment epithelium (RPE) and outer retinal atrophy in extensive macular atrophy with pseudodrusen-like appearance. METHODS: Three-year, prospective, observational study. Nine patients with extensive macular atrophy with pseudodrusen-like appearance (17 eyes; 6 women) with no other ocular conditions were annually examined; one eye was excluded because of macular neovascularization. Best-corrected visual acuity measurement, fundus photographs, blue-light autofluorescence, and optical coherence tomography were performed at each visit. Formation of atrophy was analyzed on optical coherence tomography at foveal and extrafoveal areas following the Classification of Atrophy Meeting recommendations. Spatial enlargement throughout four sectors was assessed on blue-light autofluorescence after placing an Early Treatment for Diabetic Retinopathy Study grid centered on the foveola. RESULTS: Mean age was 53.0 ± 2.1 years at baseline with a follow-up of 36.6 ± 0.7 months. Thinning of the outer nuclear layer and disruption of the ellipsoid zone initially appeared above areas of RPE-Bruch membrane separation and preceded RPE atrophy. Subfoveal fibrosis was seen in 65% of the eyes. Superior sector involvement was found in all patients at baseline and was significantly larger than the other sectors at any time point ( P < 0.001). Best-corrected visual acuity declined from 68.0 ± 15.7 letters to 44.8 ± 14.9 letters during the follow-up and was significantly associated with subfoveal atrophy ( P < 0.001) and fibrosis ( P = 0.02). CONCLUSION: Our findings suggest that primary alterations in patients with extensive macular atrophy with pseudodrusen-like appearance are present at the outer segment-RPE interface, with the superior Early Treatment for Diabetic Retinopathy Study sector being the most vulnerable, which progresses to extensive atrophy of the RPE and outer retinal layers. Accordingly, we propose a three-stage disease classification.

CORRELATION BETWEEN INFLAMMATORY FOCI REACTIVATION AND ATROPHY GROWTH IN EYES WITH IDIOPATHIC MULTIFOCAL CHOROIDITIS.

PURPOSE: To correlate the number of inflammatory reactivations in atrophic foci of multifocal choroiditis (MFC) with their growth rate over a 4-year span. METHODS: Comparative case series. Optical coherence tomography scans of patients affected by MFC were reviewed to identify reactivations within or at the margin of atrophic MFC foci. The area of selected lesions was semiautomatically delineated on fundus autofluorescence images and recorded at yearly intervals for a total follow-up of 4 years. The main outcome was the difference in annual square-root transformed area growth rate between lesions that reactivated and lesions that did not. RESULTS: Sixty-six foci of 30 eyes of 24 patients were included. All MFC foci enlarged over time, but the annual growth rate was more than double in lesions that reactivated compared with those that did not (mean [SD], 0.051 [0.035] vs. 0.021 [0.015] mm/year, P < 0.001), despite starting from comparable baseline areas. For each additional inflammatory reactivation, the annual growth rate increased by more than 20% (+0.009 mm/year, 95% CI [0.006, 0.012], P < 0.001). CONCLUSION: Increasing number of reactivations of atrophic foci led to proportional increments in their growth rate, highlighting the need for a tight control of inflammatory relapses in patients affected by MFC.

LONGITUDINAL FOLLOW-UP OF CHOROIDAL GRANULOMAS WITH INDOCYANINE GREEN ANGIOGRAPHY AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY: A Lesion-Based Analysis.

PURPOSE: To investigate choroidal granulomas visualized by indocyanine green angiography (ICGA) and optical coherence tomography angiography (OCTA) in response to treatment. METHODS: Ten eyes of eight patients with tubercular, sarcoid, or Vogt-Koyanagi-Harada-associated choroidal granulomas were evaluated in this multicentric study. All patients underwent ICGA and OCTA at baseline, 1, and 3 months after treatment onset. Granulomas were identified as hypofluorescent lesions on intermediate ICGA phases. Late ICGA behavior and OCTA visualization were assessed. RESULTS: On baseline intermediate ICGA, 222 choroidal granulomas were detected. Overall, 174/222 granulomas were detected on baseline OCTA images. At 1 month, 28% of lesions were healed and 48 late ICGA hyperfluorescent lesions were identified. At 3 months, 63% of baseline lesions were healed, with 33 persistent late hyperfluorescent lesions. Optical coherence tomography angiography sensitivity was reduced at 1 and 3 months compared with baseline. Some flow-voids detected on OCTA at 1 and 3 months did not correspond to any visible lesion on ICGA. CONCLUSION: Different healing behaviors of choroidal granulomas were identified combining ICGA and OCTA analysis. Late ICGA hyper-fluorescent lesions may be the consequence of a possible fibrotic shift. Structural changes in the choroid may persist after active granulomas resolution resulting in persistent flow voids on OCTA.

Acute Posterior Ocular Toxoplasmosis: An Optical Coherence Tomography Angiography and Dye Angiography Study.

PURPOSE: To compare Indocyanine Green (ICGA) and fundus fluorescein angiography (FFA) with Optical Coherence Tomography Angiography (OCTA) findings in toxoplasmic chorioretinitis (TCR). METHODS: Patients affected by active TCR were included. FFA, ICGA, and OCTA images were analyzed and lesions were compared between different modalities. Satellite dark dots (SDD) were compared between modalities. RESULTS: Fifteen patients were enrolled. The mean lesion area was similar between fundus photography (FP), FFA, and OCTA-Retina. The mean lesion area was similar between ICGA and OCTA-Choroid slab. ICGA and OCTA-Choroid showed a larger extension of the lesion compared to FP, FFA, and OCTA-Retina (p = .01, 0.0001, and 0.0002 for ICG angiography and p = .03, 0.008, and 0.0002 for OCTA-Choroid, respectively). On OCTA B-scans, the retinal flow defects were smaller than the underlying choroidal non-perfusion. The number of SDD was similar between ICGA and OCTA. CONCLUSIONS: OCTA is a reliable method to assess retinal and choroidal involvement in TCR. OCTA confirmed a wider involvement of the choroid than the retina.

Optical Coherence Tomography Angiography Findings of Iris Ischemia and Reperfusion in Cytomegalovirus Panuveitis.

PURPOSE: To report a case of iris ischemia in an eye affected by Cytomegalovirus (CMV)-related Chronic Retinal Necrosis (CRN) with partial reperfusion after antiviral therapy demonstrated by optical coherence tomography angiography (OCTA). METHODS: Retrospective case report. Multimodal imaging was performed at each follow-up visits. RESULTS: At baseline, the clinical findings and PCR on aqueous confirmed the diagnosis of CMV-induced CRN, while OCTA and Fluorescein Angiography showed multi-sectoral retinal and iris non-perfusion. After three weekly intravitreal injections of Foscarnet and retinal photocoagulation, the clinical and angiographic picture improved, with partial reperfusion of both retinal and iris vasculature. CONCLUSION: Retinal and iris non-perfusion in CRN can be partially reversible, if prompt treatment is administered. OCTA of the anterior segment allowed an accurate follow-up of the iris vasculature and its perfusion.

Progression of Atrophy and Visual Outcomes in Extensive Macular Atrophy with Pseudodrusen-like Appearance.

Purpose: To report visual outcomes and rate of retinal pigment epithelium (RPE) atrophy progression in patients with extensive macular atrophy with pseudodrusen-like appearance (EMAP). Design: Retrospective, observational study. Participants: Patients with EMAP and symptom onset before 55 years of age, at least 12 months of follow-up using Spectralis blue-light fundus autofluorescence (BAF) and OCT and with no other ocular or systemic conditions. Methods: Best-corrected visual acuity (BCVA), BAF, and OCT images were reviewed at baseline and at each annual visit until the last available follow-up. Atrophy was measured by 2 graders using the region finder software on Heidelberg Explorer and confirmed using OCT scans covering the entire atrophic lesion. The following imaging biomarkers were analyzed at each visit: foveal atrophy, vitreomacular traction, outer retinal tubulations, choroidal caverns and subfoveal choroidal thickness, border autofluorescence pattern (hyper-autofluorescent or iso-autofluorescent), and border irregularity as expressed by circularity index (CI). Main Outcome Measures: Primary outcomes were annual rate of atrophy enlargement and BCVA loss in EMAP patients. Secondary outcomes included the assessment of potential factors able to predict disease progression. Results: Thirty-six eyes from 18 patients with EMAP (6 men [33%]; mean age at symptom onset, 48.1 ± 1.7 years) were included. Mean follow-up lasted 32.8 ± 14.3 months. RPE atrophy increased from 10.8 ± 6.3 mm2 at baseline to 18.1 ± 8.3 mm2 at the end of follow-up, with a rate of 2.91 ± 1.09 mm2/year. Faster progression was associated with smaller CI at baseline (P = 0.02) and with iso-autofluorescent lesion borders (P = 0.01). Visual acuity declined progressively at a rate of 7.4 ± 5.8 letters per year, with 57% of eyes showing vision of 20/200 Snellen or worse at the 4-year follow-up. Worse visual outcomes were observed in patients with early foveal involvement at baseline (P = 0.02). Conclusions: Patients affected by EMAP present a rapid expansion of RPE atrophy that is comparable with the diffuse-trickling form of geographic atrophy. More irregular and iso-autofluorescent lesion borders seem to predict faster progression. Our findings may provide relevant information for patient counseling and future interventional approaches to select the best candidates and proper clinical outcomes.

Retinal findings in patients with COVID-19: Results from the SERPICO-19 study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been associated to microvascular alterations. We screened the fundus of patients with COVID-19 to detect alterations of the retina and its vasculature and to assess possible correlations with clinical parameters. METHODS: Cross-sectional study. The presence of retinal alterations in patients with COVID-19 and subjects unexposed to the virus was assessed using fundus photographs and their prevalence was compared. Mean arteries diameter (MAD) and mean veins diameter (MVD) were compared between patients and unexposed subjects with multiple linear regression including age, sex, ethnicity, body mass index, smoking/alcohol consumption, hypertension, hyperlipidaemia, diabetes as covariates. The influence of clinical/lab parameters on retinal findings was tested in COVID-19 patients. FINDINGS: 54 patients and 133 unexposed subjects were enrolled. Retinal findings in COVID-19 included: haemorrhages (9·25%), cotton wools spots (7·4%), dilated veins (27·7%), tortuous vessels (12·9%). Both MAD and MVD were higher in COVID-19 patients compared to unexposed subjects (98·3 ± 15·3 µm vs 91·9 ± 11·7 µm, p = 0.006 and 138·5 ± 21·5 µm vs 123·2 ± 13·0 µm, p<0.0001, respectively). In multiple regression accounting for covariates MVD was positively associated with COVID-19 both in severe (coefficient 30·3, CI95% 18·1-42·4) and non-severe (coefficient 10·3, CI95% 1·6-19·0) cases compared to unexposed subjects. In COVID-19 patients MVD was negatively correlated with the time from symptoms onset (coefficient -1·0, CI 95% -1·89 to -0·20) and positively correlated with disease severity (coefficient 22·0, CI 95% 5·2-38·9). INTERPRETATION: COVID-19 can affect the retina. Retinal veins diameter seems directly correlated with the disease severity. Its assessment could have possible applications in the management of COVID-19. FUNDING: None.

Presenting Features, Treatment and Clinical Outcomes of Cytomegalovirus Retinitis: Non-HIV Patients Vs HIV Patients.

PURPOSE: To compare clinical features, complications, and outcomes of CMV retinitis in non-HIV immunocompromised patients with HIV infected patients. METHODS: A retrospective study of patients diagnosed with CMV retinitis with or without HIV infection was performed. Results: Thirty-five eyes from 27 patients (median follow up 26 months) were included. Six patients had HIV infection, the others were immunocompromised from a range of causes. The baseline visual acuity (VA) was similar in the two groups. Prevalence of different types of retinitis (fulminant/indolent) was similar in the two groups. Presence of vitreous haze ≥1+ (p = .041), presence of arteritis, (p = .016) and widespread vascular occlusion (p = .003) were more common in the non-HIV group. CONCLUSION: CMV retinitis can present with different features depending on the cause of immunocompromise. Evidence of intraocular inflammation such as vitritis, retinal arteritis, and vascular occlusions was more common in HIV-negative subjects.

MACULAR HOLE IN A YOUNG PATIENT AFFECTED BY FAMILIAL EXUDATIVE VITREORETINOPATHY.

PURPOSE: To report a case of familial exudative vitreoretinopathy in which genetic testing was used to confirm the diagnosis with a new mutation identified in FZD4 gene. METHODS: A 28-year-old girl was addressed to our clinic for surgical management of a macular hole possibly associated with Coats disease. Multimodal imaging was performed including fundus photography, fundus autofluorescence, optical coherence tomography, fluorescein, and indocyanine green angiography. RESULTS: On examination, visual acuity was light perception secondary to previous retinal detachment and 20/32, respectively, in her right and left eye. Clinical and imaging evaluations showed findings suggestive for familial exudative vitreoretinopathy. Spectral domain optical coherence tomography study of the macula showed a macular pucker with lamellar macular hole and a conservative approach was preferred. After 18 months of observation, the patient underwent surgery secondary to the onset of a full thickness macular hole. After 24 months, the patient's vision was 20/32. Genetic testing was used to confirm the diagnosis demonstrating 2 new mutations in FZD4 gene. CONCLUSION: Our case emphasizes the importance of a prompt recognition of familial exudative vitreoretinopathy disease also using gene testing and a close follow-up to prevent and manage possible complications.

Pathogenicity of new BEST1 variants identified in Italian patients with best vitelliform macular dystrophy assessed by computational structural biology.

BACKGROUND: Best vitelliform macular dystrophy (BVMD) is an autosomal dominant macular degeneration. The typical central yellowish yolk-like lesion usually appears in childhood and gradually worsens. Most cases are caused by variants in the BEST1 gene which encodes bestrophin-1, an integral membrane protein found primarily in the retinal pigment epithelium. METHODS: Here we describe the spectrum of BEST1 variants identified in a cohort of 57 Italian patients analyzed by Sanger sequencing. In 13 cases, the study also included segregation analysis in affected and unaffected relatives. We used molecular mechanics to calculate two quantitative parameters related to calcium-activated chloride channel (CaCC composed of 5 BEST1 subunits) stability and calcium-dependent activation and related them to the potential pathogenicity of individual missense variants detected in the probands. RESULTS: Thirty-six out of 57 probands (63% positivity) and 16 out of 18 relatives proved positive to genetic testing. Family study confirmed the variable penetrance and expressivity of the disease. Six of the 27 genetic variants discovered were novel: p.(Val9Gly), p.(Ser108Arg), p.(Asn179Asp), p.(Trp182Arg), p.(Glu292Gln) and p.(Asn296Lys). All BEST1 variants were assessed in silico for potential pathogenicity. Our computational structural biology approach based on 3D model structure of the CaCC showed that individual amino acid replacements may affect channel shape, stability, activation, gating, selectivity and throughput, and possibly also other features, depending on where the individual mutated amino acid residues are located in the tertiary structure of BEST1. Statistically significant correlations between mean logMAR best-corrected visual acuity (BCVA), age and modulus of computed BEST1 dimerization energies, which reflect variations in the in CaCC stability due to amino acid changes, permitted us to assess the pathogenicity of individual BEST1 variants. CONCLUSIONS: Using this computational approach, we designed a method for estimating BCVA progression in patients with BEST1 variants.

The Incidence of Neovascularization in the Fellow Eye of Patients with Unilateral Choroidal Lesion: A Survival Analysis.

PURPOSE: To compare the difference in the rate of survival of unaffected fellow eyes between choroidal neovascularization (CNV) in the first eyes and retinal angiomatous proliferation (RAP) in the first eyes. DESIGN: Cohort retrospective study. PARTICIPANTS: A total of 329 consecutive patients enrolled in our Eye Clinic between February 2006 and November 2014 were involved in the study. Only patients with naïve unilateral forms of neovascularization in 1 eye were included in this study. METHODS: A clinical database containing patients' data and ocular history was evaluated. Only patients with naive lesions in 1 eye and without signs of neovascular AMD in the fellow eye were included in the analysis. The time of absence of neovascularization in the fellow eye was calculated. MAIN OUTCOME MEASURES: Survival of the fellow eye was estimated by Kaplan-Meier analysis, and log-rank test was used to compare CNV and RAP fellow eye survival. RESULTS: A total of 202 eyes affected by CNV and 39 eyes affected by RAP were enrolled in the study. The mean follow-up time was 2.9 years (range, 182-2461 days) for CNV and 2.6 years (range, 519-1504 days) for RAP. Kaplan-Meier analysis showed that the 50% of the fellow eyes with CNV did not develop neovascularization for 5.3 years, whereas the 50% of the fellow eyes with RAP did not develop neovascularization for 3.5 years. Log-rank test showed a highly significant difference between the 2 curves (P < 0.002). CONCLUSIONS: This study showed that the incidence of neovascularization in the unaffected fellow eye increases with time, and when the first eye is affected by RAP, the development of a lesion in the second eye is more premature.

COMPARISON AMONG DIFFERENT DIAGNOSTIC METHODS IN THE STUDY OF TYPE AND ACTIVITY OF CHOROIDAL NEOVASCULAR MEMBRANES IN AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To determine interobserver and intraobserver agreement in classifying the subtypes of choroidal neovascularization (CNV) and the decision of retreatment in patients affected by exudative age-related macular degeneration. Different imaging techniques were evaluated individually and compared with multiimaging. METHODS: Fifty-two patients with naive CNV in age-related macular degeneration were evaluated after 3 monthly intravitreal injections of ranibizumab. Choroidal neovascularization subtype and activity were evaluated using spectral domain optical coherence tomography, infrared light, fundus autofluorescence, fluorescein angiography (FA), and indocyanine green angiography (ICGA). The evaluation was performed independently by 10 different retina specialists, 2 for each test. Other two operators analyzed all the information available together. RESULTS: The interobserver k regarding the types of CNV was 0.69 for multiimaging, 0.63 for spectral domain optical coherence tomography, 0.43 for FA, and 0.46 for ICGA. The k values for interobserver for retreatment decision were 0.77 for multiimaging, 0.88 for spectral domain optical coherence tomography, 0.61 for infrared, 0.37 for fundus autofluorescence, 0.25 for FA, and 0.23 for ICGA. Fluorescein angiography, spectral domain optical coherence tomography, ICGA, and infrared showed good association with multiimaging on defining CNV activity (P = 0.0003, P < 0.0001, P = 0.01, and P = 0.05, respectively). CONCLUSION: Optical coherence tomography and infrared evaluations of CNV activity were reproducible and strongly associated with multiimaging, whereas FA and ICGA evaluations showed poor reproducibility.

OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN CYTOMEGALOVIRUS RETINITIS: A Longitudinal Study.

PURPOSE: To evaluate the vitreal, retinal, and choroidal features using spectral domain optical coherence tomography (SD-OCT) in eyes affected by cytomegalovirus (CMV) retinitis. METHODS: Patients diagnosed with either active or inactive CMV retinitis were included in the study. Complete ophthalmic examination, serial color fundus photography, and SD-OCT (with and without enhanced depth imaging function) were performed for all the subjects at baseline and follow-up visits. The SD-OCT images were analyzed by two independent graders to evaluate the structural changes in areas of CMV retinitis. Prevalence data for vitreal, retinal, and choroidal SD-OCT features were collected. RESULTS: Twelve eyes from 9 patients (6 males, mean age: 52.7 ± 10.3 years) were enrolled. Nine eyes were diagnosed with active CMV retinitis at baseline. Active disease SD-OCT characteristic findings included nebulous vitritis (100%), posterior hyaloid thickening (83.3%), epiretinal membrane (100%), and retinal swelling (100%). Two distinct patterns of chorioretinal involvement were observed in active retinitis: 1) full-thickness retinitis (Full thickness retinitis) (n = 7 eyes) with choriocapillaris alterations and retinal pigment epithelial thickening and 2) cavernous retinitis (n = 3 eyes) characterized by inner retinal hyperreflectivity, large empty spaces in outer nuclear layer, and bridges of retinal tissue but retinal pigment epithelium and choriocapillaris sparing. Patients with cavernous retinitis develop retinal detachment during follow-up. Eyes with Full thickness retinitis developed choriocapillaris atrophy and choroidal thinning and retinal scars as the lesions healed. CONCLUSION: There are two distinct patterns of chorioretinal involvement in CMV retinitis. SD-OCT is a useful tool in the diagnosis, management, and prediction of the outcome of CMV retinitis.

Correlation of Optical Coherence Tomography and Autofluorescence in the Outer Retina and Choroid of Patients With Choroideremia.

PURPOSE: To evaluate the relationships between RPE, photoreceptor, and choroidal degeneration in choroideremia. METHODS: Enhanced-depth imaging optical coherence tomography (EDI-OCT), scanning laser ophthalmoscopy (SLO), and autofluorescence (AF) were performed on 39 patients (78 eyes) with choroideremia. The edges of surviving outer retina on OCT and residual AF were aligned. The distribution of outer retinal tubulations was mapped over a range of ages (16-71 years), and comparison made between pre- and postsubretinal gene therapy. Subfoveal choroidal thickness (SFCT) was compared between 23 choroideremia patients (42 eyes) and 20 age- and refraction-matched male controls (40 eyes). RESULTS: The edges of RPE AF aligned with a reduction in outer nuclear layer thickness (Spearman's rho = 0.9992). Correlation was also found between the quality of AF and integrity of ellipsoid zone within islands of surviving retina. Tubulations existed in 71 of 78 (91%) eyes with choroideremia and remained stable following gene therapy. Subfoveal choroidal thickness was reduced at baseline in choroideremia (179.7 ± 17.2 µm) compared with controls (302.0 ± 4.8 µm; P < 0.0001), but did not undergo significant thinning until end-stage retinal degeneration (43.1 ± 6.5 µm). CONCLUSIONS: The data suggest that RPE loss is the primary cause of photoreceptor degeneration in choroideremia. The choroid is thinner than controls from early stages, in keeping with a mild developmental defect. Photoreceptors appear to lose outer segments following loss of underlying RPE and form tubulations at the edges of degeneration. The preservation of tubulations over time and after subretinal injection would be consistent with these structures maintaining attachment to the inner retina and hence being potentially light responsive (ClinicalTrials.gov, NCT01461213).

Dark Atrophy: An Optical Coherence Tomography Angiography Study.

PURPOSE: To assess the status of choriocapillaris in eyes with macular atrophy secondary to age-related macular degeneration (AMD) (geographic atrophy [GA]) and Stargardt disease (STGD) using optical coherence tomography angiography (OCTA). DESIGN: Prospective, observational case series. PARTICIPANTS: A total of 14 patients (20 eyes) affected by GA and 10 patients (20 eyes) affected by STGD. METHODS: Each patient underwent a complete ophthalmological examination including fundus autofluorescence (FAF), dynamic simultaneous fluorescein angiography (FA) and indocyanine green angiography (ICGA), enhanced-depth imaging optical coherence tomography (EDI-OCT) (HRA+OCT Spectralis, Heidelberg Engineering, Heidelberg, Germany), and OCTA using AngioVue technologies (Optovue Inc, Freemont, CA). MAIN OUTCOME MEASURES: An evaluation of the status of choriocapillaris in the 2 groups was performed. RESULTS: Patients' mean age was 75 years for subjects with GA (median, 76 years; range, 63-88 years) and 61 years for STGD (median, 62 years; range, 40-74 years). Atrophy was bilateral in 42% (n = 6) of subjects with GA and 100% (n = 10) of subjects with STGD. In the early frames, FA displayed hyperfluorescence in the atrophic area in 100% (n = 20) of eyes affected by GA and 20% (n = 4) of eyes affected by STGD; dark choroid was present in 0% of GA eyes and 65% of STGD eyes (n = 13). Atrophy in ICGA late frames was hypofluorescent in 20% (n = 4) of GA eyes and 100% (n = 20) of STGD eyes. A ring at atrophy margins was detected in both FA (90%, n = 18) and ICGA (100%, n = 20) in STGD eyes. Mean subfoveal choroidal thickness was 156 µm (147, 42-362 µm) for GA eyes and 168 µm (167, 55-320 µm) for STGD eyes (P = 0.59). At OCTA evaluation, GA eyes showed persisting, rarefied choriocapillaris in correspondence of retinal pigment epithelium (RPE) atrophy in 80% (n = 16) of cases, whereas eyes affected by STGD had disappearance of this tissue in 100% (n = 20; P < 0.0001). CONCLUSIONS: Analysis of macular atrophy by OCTA in patients with STGD revealed an extensive loss of choriocapillaris in the central area with persisting tissue at its margins, whereas in those with GA the area of RPE loss showed persistent but rarefied choriocapillaris.

Reproducibility of retinal thickness measurements on normal and pathologic eyes by different optical coherence tomography instruments.

PURPOSE: To compare retinal thickness measurements produced by different time-domain and spectral-domain optical coherence tomography (TD-OCT and SD-OCT) devices when imaging normal and pathologic eyes. DESIGN: Prospective, observational study in an academic institutional setting. METHODS: A total of 110 eyes were imaged by 6 different OCT devices: Stratus and Cirrus (Carl Zeiss Meditec Inc), Spectralis HRA+OCT (Heidelberg Engineering), RTVue-100 (Optovue Inc), SDOCT Copernicus HR (Optopol Technology S.A.), and 3D OCT-1000 (Topcon Corporation). Eyes were normal or affected by different pathologies of the retina, including exudative and nonexudative age-related macular degeneration, epiretinal membrane, cystoid macular edema, and macular hole. For each instrument we used standard analysis protocols for macular thickness evaluation. Mean retinal thickness values between the instruments in the ETDRS central circular 1000-µm-diameter areas and in the ETDRS midperipheral circular 3000-µm-diameter areas were compared. RESULTS: The 6 different devices produced measurements that differ in variance (Bartlett test, P = .006), and mean values (Friedman test, P < .001). Bland-Altman analysis revealed that the limits of agreement for all the comparisons were not acceptable. Regression was calculated and it was elaborated into a conversion table, despite a high standard error for both intercepts and slope conversion values. CONCLUSIONS: This study suggests that retinal thickness measurements obtained with various OCT devices are different beyond clinical practice tolerance, according to Bland-Altman analysis. Furthermore, regression analysis reveals high standard error values. These differences appear to be primarily attributable to the analysis algorithms used to set retinal inner and outer boundaries.