Smartphone Eye Examination: Artificial Intelligence and Telemedicine.

Background: The current medical scenario is closely linked to recent progress in telecommunications, photodocumentation, and artificial intelligence (AI). Smartphone eye examination may represent a promising tool in the technological spectrum, with special interest for primary health care services. Obtaining fundus imaging with this technique has improved and democratized the teaching of fundoscopy, but in particular, it contributes greatly to screening diseases with high rates of blindness. Eye examination using smartphones essentially represents a cheap and safe method, thus contributing to public policies on population screening. This review aims to provide an update on the use of this resource and its future prospects, especially as a screening and ophthalmic diagnostic tool. Methods: In this review, we surveyed major published advances in retinal and anterior segment analysis using AI. We performed an electronic search on the Medical Literature Analysis and Retrieval System Online (MEDLINE), EMBASE, and Cochrane Library for published literature without a deadline. We included studies that compared the diagnostic accuracy of smartphone ophthalmoscopy for detecting prevalent diseases with an accurate or commonly employed reference standard. Results: There are few databases with complete metadata, providing demographic data, and few databases with sufficient images involving current or new therapies. It should be taken into consideration that these are databases containing images captured using different systems and formats, with information often being excluded without essential detailing of the reasons for exclusion, which further distances them from real-life conditions. The safety, portability, low cost, and reproducibility of smartphone eye images are discussed in several studies, with encouraging results. Conclusions: The high level of agreement between conventional and a smartphone method shows a powerful arsenal for screening and early diagnosis of the main causes of blindness, such as cataract, glaucoma, diabetic retinopathy, and age-related macular degeneration. In addition to streamlining the medical workflow and bringing benefits for public health policies, smartphone eye examination can make safe and quality assessment available to the population.

FUNDUS AUTOFLUORESCENCE IN EXTENSIVE MACULAR ATROPHY WITH PSEUDODRUSEN AND DIFFUSE TRICKLING GEOGRAPHIC ATROPHY.

PURPOSE: To establish whether extensive macular atrophy with pseudodrusen (EMAP) can be distinguished from the diffuse-trickling phenotype of geographic atrophy (DTGA) secondary to age-related macular degeneration on the basis of its features on blue-light autofluorescence. METHODS: The authors reviewed our prospectively maintained database to enroll patients with a diagnosis of EMAP, DTGA, and non-DTGA with a minimum follow-up of 1 year. Atrophic areas and growth rates were measured on blue-light autofluorescence images, using the Heidelberg Region Finder tool. Circularity and roundness were chosen as atrophy shape descriptors, extracted using ImageJ, and compared between disease groups. RESULTS: A total of 28 EMAP, 27 DTGA, and 30 non-DTGA eyes were included in the analysis. The median follow-up time was around 3.5 years. Extensive macular atrophy with pseudodrusen was characterized by an irregular and elongated shape (low circularity and low roundness) and associated with a fast atrophy growth rate (3.6 mm 2 /year), compared with non-DTGA. However, these parameters were not significantly different between EMAP and DTGA. CONCLUSION: Our study found that EMAP and DTGA cannot be effectively differentiated on fundus autofluorescence. In both diseases, the macular atrophic area has a major vertical axis, fringed borders, and fast progression.

HYPERREFLECTIVE BAND IN THE GANGLION CELL LAYER IN RETINITIS PIGMENTOSA.

PURPOSE: To describe a sign that takes the form of a continuous hyperreflective band within the thickness of the ganglion cell layer (GCL), thus dubbed the "hyperreflective ganglion cell layer band" (HGB), which the authors detected in a fraction of patients affected by retinitis pigmentosa (RP). METHODS: Retrospective, cross-sectional, observational study. Optical coherence tomography (OCT) images of patients with RP examined between May 2015 and June 2021 were retrospectively reviewed for the presence of HGB, epiretinal membrane (ERM), macular hole, and cystoid macular edema (CME). The ellipsoid zone (EZ) width was also measured. A subgroup of patients underwent microperimetry in the central 2°, 4°, and 10°. RESULTS: One hundred and fifty-four eyes from 77 subjects were included in the study. The HGB was present in 39 (25.3%) eyes with RP. Mean best-corrected visual acuity (BCVA) was 0.39 ± 0.05 logMAR (approximately 20/50 Snellen equivalent) and 0.18 ± 0.03 logMAR (approximately 20/32 Snellen equivalent) in eyes with and without HGB, respectively ( P < 0.001). The two groups did not differ regarding EZ width; mean 2°, 4°, and 10° retinal sensitivity; and prevalence of CME, ERM, and macular hole. The multivariable analysis showed the presence of HGB to be a predictor of poorer BCVA ( P < 0.001). CONCLUSION: HGB is an OCT finding detectable in approximately a quarter of eyes with RP and is associated with a poorer visual function. In the discussion, the authors speculate about possible morphogenetic scenarios to explain this observation.

Toward an Intravoxel Incoherent Motion 2-in-1 Magnetic Resonance Imaging Sequence for Ischemic Stroke Diagnosis? An Initial Clinical Experience With 1.5T Magnetic Resonance.

OBJECTIVE: This initial study aimed to investigate the feasibility of simultaneously measuring perfusion and diffusion including kurtosis features in acute ischemic stroke with the combined intravoxel incoherent motion and non-Gaussian diffusional kurtosis imaging (DKI-IVIM). MATERIAL AND METHODS: Five ischemic stroke patients underwent a 4-minute diffusion weighted imaging (DWI) protocol, using 8 b values chosen with the Cramer-Rao-Lower-Bound optimization approach, in addition to conventional DWI and arterial spin labeling sequences. Regions of interest in pathological and control regions were analyzed with DKI-IVIM, and parametric maps were reconstructed. RESULTS: The IVIM diffusion coefficient (D) decreased (P < 0.0001) in the infarcted areas, whereas higher kurtosis coefficient values were found (P = 0.0002). Regarding the perfusion, the individual IVIM perfusion fraction f decreased in 3 matching cases with the cerebral blood flow estimated through arterial spin labeling and the fD* decreased only in 2 patients of those. CONCLUSIONS: When compared with conventional stroke imaging protocol, DKI-IVIM 4-minute 2-in-1 acquisition can provide diffusion results comparable with conventional DWI with complementary kurtosis estimations but a limited robustness regarding perfusion estimations for clinical purpose.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FINDINGS IN PIGMENTED PARAVENOUS CHORIORETINAL ATROPHY.

PURPOSE: To analyze the retino-choroidal vascular characteristics of patients affected by pigmented paravenous chorio-retinal atrophy by means of optical coherence tomography (OCT) angiography. METHODS: This study was designed as an observational, cross-sectional case series. Multimodal imaging included fundus autofluorescence, structural OCT, and OCT angiography. The quantitative OCT angiography analyses included the calculation of the vessel density and choriocapillaris porosity. RESULTS: Overall, 12 patients (24 eyes) affected by pigmented paravenous chorio-retinal atrophy were recruited. Structural OCT of the areas involved by pigmented paravenous chorio-retinal atrophy as visualized on the fundus autofluorescence showed a complete ellipsoid zone and external limiting membrane absence, with thinning of ganglion cell complex, outer nuclear layer, and outer plexiform layer, but associated with the optical partial preservation of the retinal pigment epithelium. Optical coherence tomography angiography quantitative assessment of the retinal regions affected by PPRCA, as visualized by fundus autofluorescence, was characterized by normal vessel density at the level of superficial capillary plexus but significantly altered vessel density of deep capillary plexus and choriocapillaris, with higher choriocapillaris porosity. The presence of macular atrophy was significantly correlated with worse deep capillary plexus and choriocapillaris vessel density values. Furthermore, a statistically significant correlation between the fundus autofluorescence patterns and the retinal vascular status was found. CONCLUSION: Optical coherence tomography angiography quantitative analyses in pigmented paravenous chorio-retinal atrophy demonstrate a specific impairment at the level of the deep capillary plexus, which could in turn bring about a thinning of ganglion cell complex and outer nuclear layer. The alterations at the level of the choriocapillaris and the choroid, in general, could then represent a secondary effect.

BASELINE SATTLER LAYER-CHORIOCAPILLARIS COMPLEX THICKNESS CUTOFFS ASSOCIATED WITH AGE-RELATED MACULAR DEGENERATION PROGRESSION.

PURPOSE: To assess the relationship between choroidal overall and sublayer thickness and age-related macular degeneration (AMD) stage progression. METHODS: A prospective, observational case series was performed. Two hundred and sixty-two eyes of 262 patients with different stages of AMD were imaged by optical coherence tomography. Age-related macular degeneration stage, choroidal thickness, Sattler layer-choriocapillaris complex thickness (SLCCT), and Haller layer thickness were determined at the baseline visit, at a 1-year follow-up visit, at a 2-year follow up visit, and at a final visit (performed after a mean of 5 ± 1 year from the baseline visit). RESULTS: Baseline AMD stages were distributed as follows: early AMD (30 eyes; 12%), intermediate AMD (97 eyes; 39%), and late AMD (126 eyes; 49%). At the final follow-up, AMD stages were so distributed: early AMD (14 eyes; 6%), intermediate AMD (83 eyes; 33%), and late AMD (156 eyes; 61%). Each group showed a statistically significant decrease in choroidal thickness values over the entire follow-up ( P < 0.001), and SLCCT reduction was associated with AMD progression ( P < 0.001). Moreover, SLCCT quantitative cutoffs of <20.50 µ m and <10.5 µ m were associated with a moderate and high probability of AMD progression, respectively, and SLCCT quantitative cutoffs of <18.50 µ m and <8.50 µ m implied a moderate and high probability of macular neovascularization onset, respectively. CONCLUSION: Progressive choroidal impairment contributes to AMD progression. Among choroidal layers, a reduced SLCCT is a promising biomarker of disease worsening, and its quantitative evaluation could help to identify patients at higher risk of stage advancement.

Extended depth-of-focus (EDOF) AcrySof® IQ Vivity® intraocular lens implant: a real-life experience.

PURPOSE: Extended depth-of-focus (EDOF) is a promising intraocular lens (IOL) technology for cataract surgery. The aim of the study was to report the real-life experience related to the implant of EDOF AcrySof® IQ Vivity® (Alcon Inc., USA) IOL. METHODS: The study was designed as a interventional, prospective, case series with 3 months of follow-up. Patients needing cataract surgery, without any other kind of ocular diseases, were recruited and implanted with AcrySof® IQ Vivity® IOL. We evaluated the refractive success of this IOL through complete ophthalmologic assessments and the administration of the Quality of Vision test. The main outcome measures were the refractive outcome; far, intermediate, and near vision; and Quality of Vision score. RESULTS: We included 108 eyes (54 patients; age 62 ± 5 years). Intra-operative and post-operative complications were 0%. Thirty out of 100 eyes (28%) required toric IOL. Best-corrected visual acuity improved from 0.4 ± 0.3 LogMAR to 0.0 ± 0.0 LogMAR (p < 0.01). Refractive outcome was very good for far and intermediate visions, whereas a spherical addition of at least + 1.0D was required for near vision. The mean Quality of Vision score was of 15.5 ± 6.5. The most complained visual disturbances were haloes and glares, although resulting well-tolerated. Dynamic pupillometry findings well-correlated with the amount of complained post-operative visual discomforts. CONCLUSIONS: AcrySof® IQ Vivity® IOL is a well-tolerated choice to correct far and intermediate vision. Spectacles are needed to optimize near vision. Our data strongly suggest dynamic pupillometry as a useful investigation to optimize post-operative refractive success.

SHORT-TERM MODIFICATIONS OF ELLIPSOID ZONE IN BEST VITELLIFORM MACULAR DYSTROPHY.

PURPOSE: To assess ellipsoid zone (EZ) alterations in Best vitelliform macular dystrophy using spectral-domain optical coherence tomography. METHODS: Prospective, observational case series. Forty-three patients (43 eyes) underwent complete ophthalmological examination at baseline and at 24 months: best-corrected visual acuity (BCVA), biomicroscopy, fundus photography, and spectral-domain optical coherence tomography were performed. Acquisition protocol included 19-line raster scan. Alterations in EZ were marked on spectral-domain optical coherence tomography, and the area was manually calculated on a near-infrared reflectance image. Three patterns were identified: A (decrease >0.25 mm2), B (±0.25 mm2), and C (increase >0.25 mm2). Primary outcome was to describe different patterns of EZ alteration. Secondary outcomes included their correlation with BCVA and the description of a central optically preserved islet. RESULTS: At baseline, altered EZ was identified in 40 eyes. Worse BCVA significantly correlated with larger EZ alterations but not with lesion extension on fundus photograph. Only "pattern-C" eyes unveiled BCVA worsening at follow-up. Optically preserved islet was detected in 16 eyes (37%), disclosing significantly better vision; its disappearance at follow-up (n = 7; 44% of 16 eyes) correlated with a decrease in BCVA. CONCLUSION: The assessment of EZ status might represent a valuable functional marker in Best vitelliform macular dystrophy because stable alterations and the maintenance of a central optically preserved islet are associated with better visual acuity.

QUANTITATIVE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY PARAMETER VARIATIONS AFTER TREATMENT OF MACULAR NEOVASCULARIZATION SECONDARY TO AGE-RELATED MACULAR DEGENERATION.

PURPOSE: Macular neovascularization (MNV) secondary to age-related macular degeneration can be characterized by quantitative optical coherence tomography angiography. The aim of the study was to assess the evolution of quantitative optical coherence tomography angiography parameters after 1 year of antivascular endothelial growth factor injections. METHODS: Naive age-related macular degeneration-related MNV eyes were prospectively recruited to analyze optical coherence tomography and optical coherence tomography angiography parameters, including MNV vessel tortuosity (VT) and reflectivity, at baseline and at the end of the follow-up. Macular neovascularization eyes were categorized by a MNV VT cutoff, and quantitative parameter variations were documented after 1 year of treatment. We divided MNV eyes into Group 1 (MNV VT < 8.40) and Group 2 (MNV VT > 8.40). RESULTS: Thrity naive age-related macular degeneration-related MNV eyes (30 patients) were included. Our cohort included 18 Type 1 MNV and 12 Type 2 MNV lesions. Baseline central macular thickness (411 ± 85 µm) improved to 323 ± 54 µm at 1 year (P < 0.01). Only Group 1 MNV displayed significant visual improvement. Macular neovascularization VT values remained stable over the follow-up in both subgroups. Group 2 MNV eyes showed increased MNV reflectivity and increased MNV area at the end of the follow-up. Quantitative retinal capillary plexa parameters were found to be worse in Group 2 MNV. Outer retinal atrophy occurred in 2 of the 18 eyes in MNV Group 1 (11%) and in 6 of the 12 eyes in MNV Group 2 (50%) after 1 year. Vessel density proved to be always worse in Group 2 than in Group 1. CONCLUSION: Macular neovascularization VT provides information on the blood flow and identifies two subgroups with different final anatomical and visual outcomes, regardless of the treatment effect.

Extrafoveal Müller cells detection in vivo in the human retina: A pilot study based on optical coherence tomography.

Müller cells (MC) represent a key element for the metabolic and functional regulation of the vertebrate retina. The aim of the present study was to test the feasibility of a new method for the in-vivo detection and quantification of extrafoveal MC in human retina. We developed a new approach to isolate and analyse extrafoveal MC in vivo, starting from structural optical coherence tomography data. Our pilot investigation was based on the optical properties of MC, which are known to not interfere with the light reaching the outer retinal structures. We reconstructed MC in the macular region of 18 healthy subjects and the quantitative analyses revealed ~42,000/9 mm2 cells detected. Furthermore, we included 2 patients affected by peripheral intraocular melanoma, with macular sparing, needing surgical enucleation. We used these two eyes to perform a qualitative comparison between our reconstructions and histological findings. Our study represents the first pilot investigation dedicated on the non-invasive isolation and quantification of MC, in-vivo, in human retina. Although we are aware that our study has several limitations, first of all related with the proper detection of foveal MC, because of the peculiar z-shape morphology, this approach may open new opportunities for the non-invasive in vivo analysis of MC, providing also potential useful perspectives in retinal diseases.

Natural course of the vitelliform stage in best vitelliform macular dystrophy: a five-year follow-up study.

PURPOSE: The vitelliform stage is the typical phenotypic manifestation of Best vitelliform macular dystrophy (BVMD). As yet, no study has focused specifically on the clinical changes occurring in the vitelliform stage over the follow-up. METHODS: The survey takes the form of a prospective observational study with a 5-year follow-up. Twenty-one eyes of 11 patients in the vitelliform stage were examined annually. The primary outcome was the identification of the changes in the vitelliform lesion over a 5-year follow-up. Secondary outcomes included changes in structural optical coherence tomography (OCT) parameters and the correlation with the BCVA variation over the follow-up. RESULTS: Spectral domain OCT at baseline showed one subform characterized by solid vitelliform deposition, in 81% of eyes, and another subform characterized by a combination of solid deposition and subretinal fluid, in 19% of eyes. Overall, 62% of eyes showed an increase in the area of vitelliform deposition. Once the maximal area was reached, a progressive flattening of the vitelliform deposition took place, with subsequent flattening of the vitelliform lesion and formation of subretinal fluid. Hyperreflective foci (HF) increased in number as long as the vitelliform area continued to expand, with no variation in HF when the vitelliform lesion flattened or the subretinal fluid formed. CONCLUSIONS: The vitelliform stage reveals more subforms with clinical variations over the follow-up. Our data suggest that the substage before the flattening of the lesion, thus before the so-called subretinal fluid accumulates and when the visual acuity is still high, might offer the best opportunity for an optimal therapeutic approach.

HYPERREFLECTIVE FOVEAL SPOTS IN PATIENTS WITH VITREORETINAL ANOMALIES: A Qualitative and Quantitative Analysis.

PURPOSE: To describe structural optical coherence tomography (OCT) and OCT angiography features in patients who have developed hyperreflective foveal spots with or without vitreomacular interface abnormalities or with vitreous adhesion alone. METHODS: The study design was observational and cross sectional. The presence of defined epiretinal membrane was considered an exclusion criterion. All patients underwent complete ophthalmologic examination, with structural OCT and OCT angiography acquisitions. Both qualitative and quantitative analyses of OCT angiography reconstructions were performed for superficial capillary plexus, deep capillary plexus, and choriocapillaris. RESULTS: Thirty patients (20 men; mean age, 55.2 years) showing hyperreflective foveal spots on structural OCT and 30 healthy control subjects (20 men; mean age, 54.7 years) were enrolled. Best-corrected visual acuity was 0.0 ± 0.0 logarithm of the minimum angle of resolution (20/20 Snellen) for both patients and control subjects. Following global and parafoveal/extrafoveal analyses, both superficial capillary plexus and deep capillary plexus showed significant reduction (P < 0.001). Significant superficial capillary plexus and deep capillary plexus changes were also detected in contralateral eyes (P < 0.001). CONCLUSION: Hyperreflective foveal spots might be seen as the initial effect of traction forces causing Müller cell and external retinal layer disruption, leading to the onset of vitreomacular disease. These changes also have an effect on the retinal vascular network. Further larger prospective studies are necessary to confirm our findings.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FEATURES OF FOCAL CHOROIDAL EXCAVATION AND THE CHOROIDAL STROMA VARIATIONS WITH OCCURRENCE OF EXCAVATION.

PURPOSE: To describe retinal and choroidal vascular changes, and choroidal stroma variations occurring in focal choroidal excavation (FCE). METHODS: Study design was a cross-sectional case series. Consecutive patients affected by FCE and healthy controls were recruited. All patients underwent complete ophthalmologic assessment and multimodal imaging, including structural optical coherence tomography and optical coherence tomography angiography. Choroidal thickness and stromal index were calculated from structural optical coherence tomography images. Moreover, we measured vessel density values of the superficial capillary plexus, deep capillary plexus and choriocapillaris at the level of the macula. RESULTS: Twenty-two patients (28 eyes; mean age 57.2 ± 16.4) and 28 control eyes (mean age of 56.5 ± 9.8) were included. Five patients (23%) were asymptomatic, whereas 17 patients (77%) complained of visual symptoms. FCE was associated with choroidal neovascularization in 10 eyes (35%). Choroidal stromal component was lower in FCE patients than controls, whereas choroidal thickness was unremarkable. Stromal index values calculated in the region proximal to the FCE was significantly lower than the values obtained from the external region. Deep capillary plexus vessel density was lower in FCE than controls. Choriocapillaris was altered in the region surrounding the FCE, whereas it was normal in the external region. CONCLUSION: Deep capillary plexus and choriocapillaris plexus were significantly altered in FCE patients. Moreover, choroidal stroma was significantly reduced in the areas closer to FCE compared to the surrounding choroid in patients, as well as compared to healthy controls, suggesting the hypothesis of weakening of the architectural support, creating a more friable point, which can favor FCE development.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY CAN CATEGORIZE DIFFERENT SUBGROUPS OF CHOROIDAL NEOVASCULARIZATION SECONDARY TO AGE-RELATED MACULAR DEGENERATION.

PURPOSE: Choroidal neovascularization (CNV) is a common complication of patients affected by age-related macular degeneration, showing a highly variable visual outcome. The main aim of the study was, at baseline, to perform a quantitative optical coherence tomography angiography assessment of CNV secondary to age-related macular degeneration and to assess posttreatment outcomes. METHODS: Seventy-eight naïve age-related macular degeneration-related CNV patients (39 men, mean age 78 ± 8 years) were recruited and underwent complete ophthalmologic evaluation and multimodal imaging. Several OCT and optical coherence tomography angiography parameters were collected, including vessel tortuosity and vessel dispersion (VDisp), measured for each segmented CNV. All patients underwent anti-vascular endothelial growth factor PRN treatment. Vessel tortuosity and VDisp values of CNVs were tested at baseline to establish a cutoff able to distinguish clinically different patient subgroups. RESULTS: Mean best-corrected visual acuity was 0.49 ± 0.57 (20/62) at baseline, improving to 0.31 ± 0.29 (20/41) at the 1-year follow-up (P < 0.01), with a mean number of 6.4 ± 1.9 injections. Our cohort included the following CNV types: occult (45 eyes; 58%), classic (14 eyes; 18%), and mixed (19 eyes; 24%). Observing optical coherence tomography angiography parameters, classic, mixed, and occult CNV revealed significantly different values of VDisp, with classic forms showing the highest values and the occult CNVs showing the lowest (P < 0.01); mixed forms displayed intermediate VDisp values. The ROC analysis revealed that a CNV vessel tortuosity cut-off of 8.40, calculated at baseline, enabled two patient subgroups differing significantly in visual outcomes after anti-vascular endothelial growth factor treatment to be distinguished. CONCLUSION: A baseline quantitative optical coherence tomography angiography-based parameter could provide information regarding both clinical and functional outcomes after anti-vascular endothelial growth factor treatment in age-related macular degeneration-related CNV.

HYPERREFLECTIVE FOCI AS A PATHOGENETIC BIOMARKER IN CHOROIDEREMIA.

PURPOSE: To assess hyperreflective foci (HF) number and distribution in choroideremia (CHM) using spectral domain optical coherence tomography. METHODS: Observational, cross-sectional case series. Consecutive patients and matched controls (20 eyes each) underwent best-corrected visual acuity measurement, fundoscopy, blue-light autofluorescence (BL-FAF) and spectral domain optical coherence tomography. Hyperreflective foci were assessed on a horizontal spectral domain optical coherence tomography scan, in the 500-µm area centered on the umbo, and in the 500-µm-wide areas internal (preserved border) and external (pathologic border) to the chorioretinal atrophy of CHM patients, and in the parafovea of controls. Hyperreflective foci were subclassified as retinal or choroidal. The spared central islet was measured on BL-FAF. Primary outcome was HF quantification in CHM. Secondary outcomes included their relationships with atrophy extent. RESULTS: Choroideremia eyes disclosed a significantly higher HF number across the pathologic border and in the fovea when compared with controls; in particular, these HF were primarily located in the choroid (59-87%). Moreover, choroidal HF in the pathologic border inversely correlated with the area of the preserved central islet. CONCLUSION: Hyperreflective foci might turn out to be a potential biomarker of CHM activity or severity. In this regard, we hypothesize that HF may be related to macrophages activation or progressive retinal pigment epithelium degeneration.

Anti-VEGF treatment for choroidal neovascularization complicating pattern dystrophy-like deposit associated with pseudoxanthoma elasticum.

PURPOSE: To evaluate the efficacy of intravitreal anti-VEGF injections in choroidal neovascularization (CNV) related to pattern dystrophy-like deposit in pseudoxanthoma elasticum (PXE). METHODS: One-year prospective, interventional study. Nine eyes were recruited in the ophthalmology departments of San Raffaele University and University of Barcelona. Each patient underwent best corrected visual acuity (BCVA) measurement on ETDRS chart, slit-lamp biomicroscopy, fluorescein angiography (FA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT). The protocol included a first anti-VEGF injection, followed by monthly evaluations with re-treatments based on new funduscopic hemorrhages, fluid on OCT or leakage on FA and/or ICGA. Primary outcome measures were the mean BCVA changes. Secondary outcomes included central macular thickness (CMT) variations and the number of injections needed. RESULTS: At month 12, mean BCVA significantly improved from 20/45 to 20/35 Snellen equivalent, with 3 eyes gaining at least 3 ETDRS lines. Mean CMT decreased from 297 ± 22 to 262 ± 13 µm, after 5.5 ± 4.0 injections. No leakage was observed at the end of follow-up. CONCLUSIONS: Intravitreal anti-VEGF injections represent an effective treatment for CNV related to pattern dystrophy-like deposit in PXE, with an improvement of BCVA and CMT. Mean injection number is in line with other studies performed in CNV secondary to angioid streaks.

VASCULAR ALTERATIONS REVEALED WITH OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN PATIENTS WITH CHOROIDEREMIA.

PURPOSE: Choroideremia is a rare degenerative retinal disease that causes incurable blindness. It occurs as a result of the deficiency of the X-linked CHM gene, which encodes the Rab escort protein 1 (REP1). Gene therapy has been developed to treat CHM using adeno-associated viral vectors and is currently undergoing clinical trials. Expression of the CHM gene is ubiquitous throughout the retina, and it is therefore important to identify which retinal layers are affected in the disease process. The purpose of this study was to assess in particular the choriocapillaris using optical coherence tomography angiography because this layer is difficult to see with conventional imaging techniques. METHODS: Six men with choroideremia were identified and underwent standardized optical coherence tomography angiography as part of an ethics-approved clinical study and were compared with age-matched control subjects. RESULTS: The choriocapillaris appeared normal in regions where the retinal pigment epithelium remained intact, but it was deficient elsewhere. The outer retinal vasculature showed significant changes peripherally but also some changes centrally. The inner retinal vasculature appeared unaffected by the disease process. CONCLUSION: Choroideremia is a disease in which the choriocapillaris maintains a normal structure until the loss of the overlying retinal pigment epithelium. The inner retina also appears not to be affected at the vascular level. Although this study is limited by the small number of patients eligible for inclusion in the study, the observations support the concept of targeting gene therapy to the retinal pigment epithelium and outer retina because there is no evidence of independent degeneration of the choriocapillaris.

OPTICAL COHERENCE TOMOGRAPHY AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY EVALUATION OF COMBINED HAMARTOMA OF THE RETINA AND RETINAL PIGMENT EPITHELIUM.

PURPOSE: To study multimodal imaging features of combined hamartoma of the retina and retinal pigment epithelium (CHRRPE). METHODS: Six patients (3 males, mean age 11 years) and a healthy age-matched control group made up of 15 healthy subjects (8 males, mean age 12.6 years) were included in the analysis. Complete ophthalmologic examination was performed, including best-corrected visual acuity, anterior and posterior segment slit-lamp evaluation, and tonometry. The multimodal imaging protocol included fundus images, structural optical coherence tomography (OCT), and swept-source OCT angiography (OCTA). The main outcome measures included the qualitative evaluation of both OCT and OCTA features of CHRRPE, retinal and choroidal thickness measurements, and the quantitative analysis of superficial capillary plexus, deep capillary plexus, and choriocapillaris vessel densities. RESULTS: Optical coherence tomography features of CHRRPE were examined extensively. Multiple little hyperreflective triangular outer retinal alterations were found at the CHRRPE edges in all patients; these were dubbed the "shark-teeth" sign. Optical coherence tomography angiography showed rarefaction and morphologic alterations of all retinal plexa. Moreover, quantitative analysis revealed a statistically significant decrease in superficial capillary plexus, deep capillary plexus, and choriocapillaris vessel densities in patients affected by CHRRPE compared with the control group. CONCLUSION: Optical coherence tomography and OCTA analyses allowed the accurate qualitative and quantitative analyses of CHRRPE features. Further studies are needed to better define OCTA changes of CHRRPE better and to improve our understanding of the possible causes of the shark-teeth sign.

CAPILLARY NETWORK ALTERATIONS IN X-LINKED RETINOSCHISIS IMAGED ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To assess foveal and parafoveal vasculature at the superficial capillary plexus, deep capillary plexus, and choriocapillaris of patients with X-linked retinoschisis by means of optical coherence tomography angiography. METHODS: Six patients with X-linked retinoschisis (12 eyes) and seven healthy controls (14 eyes) were recruited and underwent complete ophthalmologic examination, including best-corrected visual acuity, dilated fundoscopy, and 3 × 3-mm optical coherence tomography angiography macular scans (DRI OCT Triton; Topcon Corp). After segmentation and quality review, optical coherence tomography angiography slabs were imported into ImageJ 1.50 (NIH; Bethesda) and digitally binarized. Quantification of vessel density was performed after foveal avascular zone area measurement and exclusion. Patients were additionally divided into "responders" and "nonresponders" to dorzolamide therapy. RESULTS: Foveal avascular zone area resulted markedly enlarged at the deep capillary plexus (P < 0.001), particularly in nonresponders. Moreover, patients disclosed a significant deep capillary plexus rarefaction, when compared with controls (P: 0.04); however, a subanalysis revealed that this damage was limited to the fovea (P: 0.006). Finally, the enlargement of foveal avascular zone area positively correlated with a decline in best-corrected visual acuity (P: 0.01). CONCLUSION: Prominent foveal vascular impairment is detectable in the deep capillary plexus of patients with X-linked retinoschisis. Our results correlate with functional outcomes, suggesting a possible vascular role in X-linked retinoschisis clinical manifestations.

SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY ASSESSMENT OF FELLOW EYES IN COATS DISEASE.

PURPOSE: To assess foveal and parafoveal vasculature at superficial capillary plexus (SCP), deep capillary plexus, and choriocapillaris using optical coherence tomography angiography in the fellow eyes of patients with Coats disease. METHODS: Observational and prospective case series. Thirteen patients with unilateral Coats and 14 healthy age- and sex-matched controls were consecutively recruited at Manchester Royal Eye Hospital and the Department of Ophthalmology of San Raffaele Hospital. Both groups underwent complete ophthalmologic examination, including optical coherence tomography angiography (Topcon Corp) 3 mm × 3 mm scans. Images were imported into ImageJ software and binarized; foveal avascular zone area was manually outlined and vessel density analyzed in inner (foveal) and outer (parafoveal) areas of SCP, deep capillary plexus, and choriocapillaris. RESULTS: Fellow eyes disclosed a significant increase in the foveal vessel density of SCP (P = 0.04); in particular, superior and temporal quadrants showed more marked alterations (P = 0.02 and 0.04, respectively). Analysis of foveal avascular zone area revealed a significant enlargement in the SCP (P = 0.04). No correlation was found between fellow eyes and the stage of affected eyes. CONCLUSION: Fellow eyes of Coats patients carry quantitative foveal vascular alterations at SCP. These may represent markers of altered inner blood-retinal barrier, due to a bilateral defect in midcapillary angiogenesis.