Macular telangiectasia type 2 in a patient with Down syndrome: A possible association.

Purpose: Down syndrome (DS) is one of the most prevalent genetic diseases associated with a variety of ophthalmic disorders, including reported retinal abnormalities. Macular telangiectasia type 2 (MacTel 2) is a late-onset neurodegenerative retinal disease with a substantial genetic component. We hereby describe a case of a female with DS who presented with MacTel 2, and we discuss the possible pathways associating both entities. Observation: We report the case of a 49-year-old female with a medical history of DS and hydroxychloroquine (HCQ) intake. She was referred for HCQ retinal toxicity screening. The multimodal imaging revealed a temporal perifoveal gray area with crystal deposits on multicolor fundoscopy with parafoveal outer retinal atrophy and ellipsoid zone loss with inner retinal cavitations in both eyes on the optical Coherence Tomography (OCT) B scan. The corresponding swept-source OCT angiography confirmed the presence of bilateral macular telangiectasia. Conclusion and importance: Metabolic pathways including serine/glycine and sphingolipids are incriminated in both entities' pathogenesis suggesting a possible association, hence, the importance of raising awareness of this association. More cases are likely to be found since DS patients currently have a nearly normal lifespan. Additional retinal examination of DS adults is then necessary to look for signs of MacTel 2.

In vivo cone-photoreceptor density comparison between eyes with subretinal drusenoid deposits and healthy eyes using high magnification imaging.

PURPOSE: To compare photoreceptor density automated quantification in eyes with subretinal drusenoid deposits (SDD) and healthy controls using Heidelberg Spectralis High Magnification Module (HMM) imaging. METHODS: Twelve eyes of 6 patients with intermediate AMD, presenting with SDD were included, as well as twelve eyes of healthy controls. Individual dot SDD within the central 30° retina were examined with infrared confocal laser ophthalmoscopy, HMM, and spectral-domain optical coherence tomography (SD-OCT). Photoreceptor density analysis was performed on the best-quality image using the ImageJ Foci Picker plugin, after the removal of SDD from the HMM image. Correlations were made between the HMM quantified photoreceptor density, SD-OCT characteristics, stage, and number of SDD. RESULTS: Mean age was 75.17 ± 2.51 years in the SDD group (3 males, 3 females) versus 73.17 ± 3.15 years in the healthy control group (p = 0.2). Defects in the overlying ellipsoid zone were present on SD-OCT in 8/12 (66.66%) eyes. The mean ± standard deviation foci detected (i.e., cone photoreceptors) was 7123.75 ± 3683.32 foci/mm2 in the SDD group versus 13,253 ± 3331.00 foci/mm2 in the healthy control group (p = 0.0003). The number of SDD was associated with a reduction in foci density, p = 0.0055, r = - 0.7622. CONCLUSION: The decreased cone density in eyes with SDD may correlate with a decrease in retinal function in intermediate AMD eyes independent of neovascular complications or outer retinal pigment epithelial atrophy.

LONG-TERM PROGNOSIS OF CHOROIDAL NEOVASCULARIZATION COMPLICATING ANGIOID STREAKS.

PURPOSE: To report the very long-term visual prognosis of choroidal neovascularization complicating angioid streaks in the antivascular endothelial growth factor era. METHODS: Retrospective monocentric study aimed at analyzing patients' demographics, choroidal neovascularization features, angioid streak-associated conditions, and previous and current therapies for choroidal neovascularization. The main outcome measures were the quantitative measurement of central retinal pigment epithelial atrophy enlargement by comparing the ratio of pixels involved on automated infrared images acquired by spectral-domain optical coherence tomography and the changes in best-corrected visual acuity. The secondary outcome measures were the number of intravitreal injections and the changes in central choroidal thickness and central retinal thickness. Subgroup analyzes were performed to compare macular atrophy extent between eyes of patients with or without proven pseudoxanthoma elasticum ("PXE" or "no PXE") and between eyes previously treated or not with photodynamic therapy ("PDT" or "no PDT"). RESULTS: Thirty-three eyes of 23 patients were included. The mean best-corrected visual acuity decreased significantly from 66 ± 19 Early Treatment Diabetic Retinopathy Study letters at the time of the first antivascular endothelial growth factor injection to 52 ± 23 Early Treatment Diabetic Retinopathy Study letters at the end of the follow-up (mean follow-up duration: 109 ± 42 months, range: 47-175 months). The ratio of central retinal pigment epithelial atrophy enlargement was 201%, 110%, 240%, and 111% in the PXE, no PXE, PDT, and no PDT groups, respectively. CONCLUSION: Despite the use of antivascular endothelial growth factor agents, the very long-term prognosis appeared relatively poor, especially in patients with PXE. This study also suggests that PDT should be used with caution in the management of choroidal neovascularization in eyes with angioid streaks.

CHOROIDAL VASCULARITY INDEX IN HYDROXYCHLOROQUINE TOXIC RETINOPATHY: A Quantitative Comparative Analysis Using Enhanced Depth Imaging In Spectral Domain Optical Coherence Tomography.

PURPOSE: To investigate choroidal involvement in eyes of patients treated with hydroxychloroquine (HCQ), by quantifying the choroidal vascularity index (CVI) and other choroidal biomarkers. METHODS: Vertical enhanced depth imaging spectral domain optical coherence tomography (SD-OCT) scans were performed in eyes with either advanced-stage or mild HCQ toxic retinopathy, as well as in healthy age-matched and sex-matched controls. Based on SD-OCT scans, the subfoveal and mean choroidal thickness (ChT) was measured. The CVI, total choroidal area (TCA), luminal choroidal area (LCA), and stromal choroidal area (SCA) were calculated based on a binarization image process. These variables were computed and compared between the three groups (i.e., advanced stage, mild toxicity, and healthy controls). RESULTS: Forty-eight eyes of 47 patients under HCQ (26 eyes presented with advanced stage HCQ toxicity and 22 eyes with mild toxicity) and 34 eyes of 31 healthy controls were included. Both CVI and ChT were significantly different between the three groups ( P < 0.001, P < 0.001). When comparing the advanced stage toxicity group to healthy controls, both the subfoveal and the mean ChT were diminished ( P < 0.001). The CVI, TCA, LCA, and SCA were significantly lower in the advanced stage of toxicity group when compared with controls ( P < 0.001, <0.00001, <0.0001, and P = 0.0094, respectively). CONCLUSION: Our study suggests that eyes with HCQ toxic retinopathy, especially at advanced stages, present with choroidal impairment, giving further pathophysiological insights into the unfolding of this retinal toxicity.

Effects of Photobiomodulation in Patients Presenting with Reticular Pseudodrusen: A Retrospective Observational Case Series Study.

Background and Objectives: The purpose of this study is to describe the effects of photobiomodulation on drusen regression with patients presenting with reticular pseudodrusen (RPD). Materials and Methods: This study is a retrospective observational case series study including patients presenting with RPD who underwent treatment by photobiomodulation. All patients underwent a complete ophthalmic examination and multimodal imaging prior to treatment, including spectral-domain optical coherence tomography (SD-OCT). Eyes were treated two times per week for six consecutive weeks. Best corrected-visual acuity (BVCA) was measured prior and after treatment for all patients. The number of RPD on the SD-OCT scans centered on the macula and stages of RPD was noted at baseline and 6 months after the first treatment session. Results: Five eyes of five patients were included in the study. Mean BCVA did not change 6 months after treatment compared to baseline. Mean number of RPD per eye was 112.60 +/- 48.33 RPD at baseline and 111.6 +/- 49.29 in the same area 6 months after treatment. Changes in RPD distribution according to RPD classification were observed before and after treatment with photobiomodulation. Changes in distribution mostly concerned stages 1 and 3 RPD: Total number of stage 1 RPD was 289 and increased to 324 after treatment. Total number of stage 3 RPD was 97 at baseline and decreased to 67 6 months after treatment. Percentage of stage 1 RPD increased from 46% to 56% after treatment. Percentage of stage 3 RPD decreased from 20% to 13% after treatment. Conclusions: Changes in RPD distribution were observed before and after treatment with photobiomodulation. The number of stage 3 reticular pseudodrusen decreased while number of stage 1 reticular pseudodrusen increased after treatment.

Choriocapillaris Flow Deficits Quantification in Hydroxychloroquine Retinopathy Using Swept-Source Optical Coherence Tomography Angiography.

This study aims to quantitatively analyze choriocapillaris (CC) alterations using swept-source optical coherence tomography angiography (SS-OCTA) in eyes presenting with hydroxychloroquine (HCQ) toxic retinopathy and to compare it to patients under HCQ without toxic retinopathy and to healthy controls. For image analysis, CC en-face slabs were extracted from macular 6 × 6 mm SS-OCTA scans and a compensation method followed by the Phansalkar local thresholding was performed. Percentage of flow deficits (FD%) and other related biomarkers were computed for comparison. Fourteen eyes (7 patients) presenting with HCQ toxic retinopathy, sixty-two eyes (31 patients) under HCQ without signs of toxicity, and sixty eyes of 34 healthy controls were included. With regards to FD%, FD average size, and FD number there was a significant difference between the three groups (p < 0.05 with radius 4 and radius 8 pixels). Eyes presenting with HCQ toxicity had significantly higher FD% and average size, and a significantly lower number of FDs, with both radius 4 and 8 pixels. In conclusion, FD quantification demonstrates that CC involvement is present in HCQ toxic retinopathy, therefore giving pathophysiological insights with regards to the CC as being either the primary or secondary target of HCQ toxicity.

Quantitative Analysis of Choriocapillaris Using Swept-Source Optical Coherence Tomography Angiography in Eyes with Angioid Streaks.

Purpose: to quantitatively analyze choriocapillaris perfusion using swept-source optical coherence tomography angiography (SS-OCTA) in eyes presenting with angioid streaks in comparison with control eyes. Methods: Macular 6 × 6 mm SS-OCTA scans were retrospectively analyzed in eyes with angioid streaks and in control eyes. En face choriocapillaris flow images were compensated with en face choriocapillaris structure images, followed by the Phansalkar local thresholding method (with a window radius of four and eight pixels). Quantitative analysis was performed in the four peripheral 1 × 1 mm corners of the 6 × 6 mm SS-OCTA image to include equidistant and comparable regions. The percentage of flow deficits (FD%), the number and size of the flow deficits (FDs) and the total area of FDs were then calculated. Results: 54 eyes of 31 patients were included in the study: 27 eyes diagnosed with angioid streaks and 27 controls. Analysis of the four 1 × 1 mm peripheral corners of the 6 × 6 mm SS-OCTA image showed that eyes with angioid streaks had a higher FD% compared to the control group (47.62 ± 8.06 versus 38.90 ± 6.38 using a radius of four pixels (p < 0.001); 48.37 ± 7.65 versus 39.66 ± 6.51 using a radius of eight pixels (p < 0.001). The average size of FDs as well as the total area size of the FDs were significantly higher in eyes with angioid streaks compared to control eyes (p < 0.001). Eyes with angioid streaks present reduced choriocapillaris flow compared to control eyes. Decreased choriocapillaris perfusion may contribute, among other factors, to the development of neovascularization and atrophy in patients with angioid streaks.

Optical coherence tomography angiography quantification of choriocapillaris blood-flow after half-fluence photodynamic therapy for chronic central serous chorioretinopathy.

PURPOSE: To quantitatively analyze characteristics of choriocapillaris flow using spectral domain optical coherence tomography angiography (SD-OCTA) in eyes with chronic central serous chorioretinopathy (CSC) before and after treatment by photodynamic therapy (PDT). METHODS: Retrospective interventional study. Macular 3X3 SD-OCT scans were analyzed in eyes diagnosed with chronic CSC before and after treatment with half-fluence PDT. The choriocapillaris en face slabs were extracted from the SD-OCTA device after manual segmentation. En face choriocapillaris flow images were compensated with en face choriocapillaris structure images. Phansalkar local thresholding method was then used with a radius of 4 and 8 pixels. Percentage of flow deficits (FD%), number, size, and total area of FDs were computed for comparison, before and after treatment by half-fluence PDT. RESULTS: Mean choriocapillaris FD% before PDT was of 58.36 + / - 11.88 and of 60.82 + / - 11.08 after PDT using radius 4 pixels with no significant difference (p = 0.140). Mean choriocapillaris FD% was of 58.63 + / - 11.08 before PDT and of 60.87 + / - 10.36 after PDT using radius 8 pixels with no significant difference (p = 0.200). Similarly, no significative difference was found in number, size, and total area of FDs, before and after half-fluence PDT, using radius 4 and 8 pixels in patients with chronic CSC. CONCLUSION: Using Phansalkar local thresholding method, quantitative analysis of choriocapillaris with SD-OCTA found no significant change in choriocapillaris flow deficits before and after successful half-fluence PDT in patients with chronic CSC. Therefore, it seems that half-fluence PDT may not alter choriocapillaris perfusion, at least on a relative short-term basis.

Progression from Type 2 Macular Neovascularization to Fibrovascular Pigment Epithelial Detachment.

The aim of this study was to report unusual progression of type 2 macular neovascularization (MNV) associated with age-related macular degeneration (AMD), high myopia or angioid streaks. Retrospective multicentric observational case series data were used. Eyes that progressed from type 2 MNV secondary to AMD, high myopia or angioid streaks to fibrovascular pigment epithelial detachment (PED) were included. A total of 29 treatment-naive eyes from 29 patients with type 2 MNV secondary to AMD (n = 14), high myopia (n = 10) or angioid streaks (n = 5) that progressed to a fibrovascular PED on Spectral Domain-Optical Coherence Tomography were used. This progression occurred within 3 months after anti-VEGF therapy initiation. Logarithm of minimum angle of resolution (LogMAR) visual acuity improved significantly after anti-VEGF therapy, from 0.55 (SD ± 0.30) (20/63-20/80) at baseline to 0.30 (20/40) at 3 months, and 0.33 (20/40) at the final follow-up (mean follow up: 3.68 years). Mean number of intravitreal injections per year for patients with a total follow-up ≥ 12 months (n = 24) was 4.3 ± 2.1 per year. Progression from type 2 MNV to a fibrovascular PED may occur in patients suffering from AMD, high myopia or angioid streaks. This progression appears early after initiation of anti-VEGF therapy and is associated with a favorable visual and anatomical outcome, at least on a short follow up basis.

CHORIOCAPILLARIS FLOW IMPAIRMENT IN TYPE 3 MACULAR NEOVASCULARIZATION: A Quantitative Analysis Using Swept-Source Optical Coherence Tomography Angiography.

PURPOSE: To quantitatively analyze choriocapillaris alterations using swept-source optical coherence tomography angiography in eyes presenting with Type 3 macular neovascularization (MNV) and to compare these alterations with eyes presenting with intermediate AMD (iAMD). METHODS: Macular 3 × 3-mm swept-source optical coherence tomography angiography scans were retrospectively analyzed in eyes with Type 3 MNV and in eyes with iAMD. The choriocapillaris en face slabs were extracted from the swept-source optical coherence tomography angiography device after manual segmentation. En face choriocapillaris flow images were compensated with en face choriocapillaris structure images, followed by the Phansalkar local thresholding method using a window radius of 4 and 8 pixels. The percentage of flow deficits (FD%), the number, size, and total area of FDs were computed for comparison. A secondary analysis was performed in the four corners of the image to include equidistant regions in all eyes. RESULTS: Twenty-six Type 3 MNV eyes of 21 patients and 26 iAMD eyes of 17 patients were included. Compared with iAMD eyes, eyes with Type 3 MNV displayed a higher FD% (41.37% ± 14.74 vs. 19.80% ± 9.63 using radius 4 pixels [P < 0.001]; 45.24% ± 11.9 vs. 26.63% ± 8.96 using radius 8 pixels [P < 0.001]). The average size of FDs was significantly larger in Type 3 MNV eyes compared with iAMD eyes (P < 0.001), whereas the number of FDs was significantly lower in Type 3 MNV compared with iAMD eyes (P < 0.001). CONCLUSION: Type 3 MNV eyes present with increased choriocapillaris flow impairment compared with iAMD eyes. Reduced choriocapillaris perfusion may contribute to Type 3 MNV development and pathogenesis.

Clinical and functional analyses of AIPL1 variants reveal mechanisms of pathogenicity linked to different forms of retinal degeneration.

Disease-causing sequence variants in the highly polymorphic AIPL1 gene are associated with a broad spectrum of inherited retinal diseases ranging from severe autosomal recessive Leber congenital amaurosis to later onset retinitis pigmentosa. AIPL1 is a photoreceptor-specific co-chaperone that interacts with HSP90 to facilitate the stable assembly of retinal cGMP phosphodiesterase, PDE6. In this report, we establish unequivocal correlations between patient clinical phenotypes and in vitro functional assays of uncharacterized AIPL1 variants. We confirm that missense and nonsense variants in the FKBP-like and tetratricopeptide repeat domains of AIPL1 lead to the loss of both HSP90 interaction and PDE6 activity, confirming these variants cause LCA. In contrast, we report the association of p.G122R with milder forms of retinal degeneration, and show that while p.G122R had no effect on HSP90 binding, the modulation of PDE6 cGMP levels was impaired. The clinical history of these patients together with our functional assays suggest that the p.G122R variant is a rare hypomorphic allele with a later disease onset, amenable to therapeutic intervention. Finally, we report the primate-specific proline-rich domain to be dispensable for both HSP90 interaction and PDE6 activity. We conclude that variants investigated in this domain do not cause disease, with the exception of p.A352_P355del associated with autosomal dominant cone-rod dystrophy.

IDIOPATHIC FOVEAL HYPOPLASIA: Quantitative Analysis Using Optical Coherence Tomography Angiography.

PURPOSE: To evaluate vascular density (VD), fractal dimension, and skeletal density on optical coherence tomography angiography in eyes with idiopathic foveal hypoplasia (IFH). METHODS: Patients presenting with IFH to Creteil University Eye Clinic between January 2015 and October 2018 and age-matched healthy controls were retrospectively evaluated. Vascular density, skeletal density, and fractal dimension analyses were computed on optical coherence tomography angiography superficial capillary plexa (SCP) and deep capillary plexa (DCP) images on the whole image using a custom algorithm. Vascular density on the central 1 mm and the peripheral 8 mm for the two groups was performed. RESULTS: Thirty-six eyes of 21 patients (18 eyes with IFH and 18 control eyes) were included. A decrease of VD at the level of the SCP and DCP was found in eyes with IFH compared with healthy control eyes (P = 0.005 for VD at the level of the SCP and P = 0.003 for VD at the level of the DCP, respectively). On the central 1 mm, VD was decreased in healthy eyes (32.3% ± 4.8) at the level of the SCP compared to IFH eyes (55.6% ± 46.3) (P < 0.001). Skeletal density was decreased in IFH eyes in both SCP and DCP (P =< 0.001). Fractal dimension was lower in IFH eyes in both SCP and DCP (P < 0.001). CONCLUSION: Vascular density, skeletal density, and fractal dimension are reduced at the level of SCP and DCP in patients with IFH compared with controls, reflecting a particular anatomical and vascular organization. Quantitative analysis using optical coherence tomography angiography could help to evaluate the severity of IFH.

INSIGHTS INTO PERIFOVEAL EXUDATIVE VASCULAR ANOMALOUS COMPLEX.

PURPOSE: To report a series of eight patients with perifoveal exudative vascular anomalous complex imaged with optical coherence tomography angiography and the results of anti-vascular endothelial growth factor therapy or laser photocoagulation. METHODS: Retrospective analysis of demographic data, imaging including color pictures, spectral domain optical coherence tomography, and optical coherence tomography angiography, and fluorescein angiography, course, and outcome. RESULTS: Age at onset ranged from 45 to 84 years (mean ± SD: 68.6 ± 13.7). Five cases were initially misdiagnosed. The perifoveal exudative vascular anomalous complex lesion was unique in seven eyes and located predominantly in the superficial capillary plexus in two eyes, strictly in the deep capillary plexus in two eyes, but observed at the level of both plexi (3 eyes). One patient presented two lesions, one in the superficial capillary plexus and one in the deep capillary plexus. Capillary rarefaction was observed around the lesion in six eyes. Sustainable resolution of exudation could be achieved in 2 patients, one after 2 sessions of focal thermal laser photocoagulation and one after 13 intravitreal injections of anti-vascular endothelial growth factor. CONCLUSION: The present series confirms that perifoveal exudative vascular anomalous complex corresponds to a new entity that differs from other conditions associated with capillary aneurysmal lesions. Visual improvement could be obtained after treatment with focal laser or intravitreal anti-vascular endothelial growth factor agents.

Chronic Herpetic Retinitis: Clinical Features and Long-Term Outcomes.

INTRODUCTION: Chronic uveitis treated with immunosuppressive agents may have unfavorable outcomes due to delays in diagnosis. The aim of this study was to review initial data from clinical and ocular assessments and patient outcomes following specific treatments for atypical herpes virus ocular infections. METHODS: The records of four consecutive patients with recurrent uveitis for at least five years treated in our department between 2001 and 2016 were retrospectively reviewed. They had atrophic retinal lesions resulting in an unfavorable outcome with lesion progression and vision loss under immunosuppressive treatment. Varicella zoster virus (1 case) and herpes simplex virus type 2 (3 cases) were detected in ocular samples. RESULTS: Uveitis was granulomatous and bilateral (3 cases) or unilateral (1 case). Immunosuppressive treatments worsened the clinical situation whereas antiherpetic treatments improved the control of intraocular inflammation. CONCLUSION: This description should be added to the broad repertoire of clinical polymorphisms associated with herpes virus infections. Recognizing these cases should be useful due to their sensitivity to antiherpetic treatments.

Association of Microvascular Function and Endothelial Biomarkers With Clinical Outcome in Dengue: An Observational Study.

BACKGROUND: The hallmark of severe dengue is increased microvascular permeability, but alterations in the microcirculation and their evolution over the course of dengue are unknown. METHODS: We conducted a prospective observational study to evaluate the sublingual microcirculation using side-stream dark-field imaging in patients presenting early (<72 hours after fever onset) and patients hospitalized with warning signs or severe dengue in Vietnam. Clinical findings, microvascular function, global hemodynamics assessed with echocardiography, and serological markers of endothelial activation were determined at 4 time points. RESULTS: A total of 165 patients were enrolled. No difference was found between the microcirculatory parameters comparing dengue with other febrile illnesses. The proportion of perfused vessels (PPV) and the mean flow index (MFI) were lower in patients with dengue with plasma than those without leakage (PPV, 88.1% vs 90.6% [P = .01]; MFI, 2.1 vs 2.4 [P = .007]), most markedly during the critical phase. PPV and MFI were correlated with the endothelial activation markers vascular cell adhesion molecule 1 (P < .001 for both) and angiopoietin 2 (P < .001 for both), negatively correlated. CONCLUSIONS: Modest microcirculatory alterations occur in dengue, are associated with plasma leakage, and are correlate with molecules of endothelial activation, angiopoietin 2 and vascular cell adhesion molecule 1.