ULTRAWIDEFIELD PSEUDOCOLOR RETINAL IMAGING VERSUS REAL-COLOR FUNDUS PHOTOGRAPHY FOR DETECTION OF INTRARETINAL PIGMENT MIGRATION IN AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To compare pseudocolor Optos ultrawidefield (UWF) retinal images with conventional real-color fundus photography (CFP) for detecting macular hyperpigmentary changes in intermediate age-related macular degeneration. METHODS: This retrospective study included 50 patients diagnosed with intermediate age-related macular degeneration. All patients underwent Optos imaging and CFP. The overall accuracy to visualize hyperpigmentation and its morphologic features was graded by two independent readers using a standardized grid. Structural and en face optical coherence tomography images were correlated with UWF and CFP images to determine spatial correspondence of pigment clumping on fundus images and hyperreflective foci on optical coherence tomography. RESULTS: One hundred eyes of 50 patients had hyperpigmentary changes on funduscopic examination and were included. The intragraders and intergraders agreements were high for all measurements (P < 0.001). At least one hyperpigmentary changes within the standardized grid was detected in 93% using CFP and 100% using UWF camera (P = 0.02). The total area of hyperpigmentation measured on UWF images was significantly higher than on CFP images (P < 0.001). There was a significant correlation between the presence of hyperpigmentary changes on both CFP and UWF images and hyperreflective foci on structural optical coherence tomography (P < 0.001). CONCLUSION: Ultrawidefield fundus images allow high detection and accurate quantification of macular hyperpigmentary changes in intermediate age-related macular degeneration compared with conventional CFP.

Pigmented paravenous retinochoroidal atrophy associated with Vogt-Koyanagi-Harada disease: a case report.

BACKGROUND: To describe a unique case of pigmented paravenous retinochoroidal atrophy that developed several years after Vogt-Koyanagi-Harada disease. CASE PRESENTATION: A 28-year-old woman presented with gradual vision loss in both eyes and nyctalopia for 2 years. Past medical history was relevant for Vogt-Koyanagi-Harada disease since the age of 19 and positive HLA-DR4. Funduscopic examination revealed perivascular pigmentary clumping and atrophic changes radiating from the optic disks. Spectral domain optical coherence tomography through the macula demonstrated perifoveal outer retinal layers loss with cystic degeneration. Fundus autofluorescence showed zonal areas of hypoautofluorescence corresponding to the areas of atrophy. Full-field electroretinogram identified mildly reduced scotopic and photopic responses. The patient was diagnosed with pigmented paravenous retinochoroidal atrophy. CONCLUSIONS: Pigmented paravenous retinochoroidal atrophy may be acquired after Vogt-Koyanagi-Harada disease. Pathogenesis of pigmented paravenous retinochoroidal atrophy may involve inflammatory-related precursors on a background of genetic predisposition.

Paracentral Acute Middle Maculopathy as a Specific Sign of Arteritic Anterior Ischemic Optic Neuropathy.

PURPOSE: The purpose of this study is to assess the diagnostic accuracy of paracentral acute middle maculopathy (PAMM) in the setting of anterior ischemic optic neuropathy (AION) to distinguish arteritic (A-AION) from nonarteritic (NA-AION) type. DESIGN: Retrospective cross-sectional diagnostic evaluation. METHODS: PAMM was evaluated by 3 physicians blinded to diagnosis using macular spectral-domain optical coherence tomography. We studied 45 patients with AION. Of those, 28 had NA-AION and 17 had A-AION. The study was conducted in the Department of Ophthalmology at the Hospital of Marseille-Assistance Publique, France, from January 1, 2018, to March 31, 2022. RESULTS: PAMM were only found in the A-AION group (N = 4) (P = .0143). As a distinctive sign of A-AION, we found a specificity of 100% (95% IC, 88.06%-100%) and a positive predictive value of 100%. In contrast, sensitivity and negative predictive value were lower, 19.1% (95% IC, 5.5-42.0) and 63.0% (95% CI, 58.1-67.7), respectively. CONCLUSIONS: The PAMM finding is highly specific for A-AION in the setting of AION. According to our results, macular spectral-domain optical coherence tomography looking for PAMM should be performed with any patient presenting with AION.

Aflibercept in real-life for the treatment of age-related macular degeneration using a treat and extend protocol: The Armada study.

PURPOSE: To report the visual and anatomic outcomes in treatment-naïve neovascular age-related macular degeneration (nAMD) patients treated with aflibercept under a standardized Treat and Extend (T&E) protocol for up to 3 years of follow-up in "real-life" practice. METHODS: This retrospective, observational, multicenter study included patients with treatment-naïve nAMD and at least 12 months of follow-up. T&E regimen adjustment was initiated after loading phase. At each visit best-corrected visual acuity (BCVA) and optical coherence tomography parameters were performed. RESULTS: One hundred and thirty-six eyes of 115patients had at least 1 year of follow-up with 114 and 82 eyes completing at least 2 and 3 years of follow-up, respectively (mean follow-up duration: 2.7 ± 1.3 years). Mean age was 78.6 ± 8.6 years old and 52% were women. Mean BCVA increased from 60.6 ± 18.7 letters at diagnosis to 66.9 ± 16.2 letters at 1 year (+6.3 letters, p = 0.003) and remained stable throughout the follow-up period (63.1 ± 20.3 letters (+2.5, p = 0.1) and 64.0 ± 20.1 letters (+3.4, p = 0.27) at 2 and 3 years, respectively). The mean central retinal thickness decreased significantly from 358.2 ± 87.9 µm at baseline to 302 ± 71.7 µm at 12 months and maintained stable after 36 months of follow-up (297.1 ± 76 µm, p < 0.0001). Mean number of injections was 6.6 ± 2.2, 4.8 ± 1.9, and 5.6 ± 1.7 at 1, 2, and 3 years, respectively. Mean cumulative number of 16.4 ± 5.6 injections after 3 years. Mean treatment interval was 6.8 ± 2.5 weeks at 1 year. Eight-week and 12-week treatment interval were achieved in 59.5% and 19.1%, 65.8%, and 36.8% and 69.5% and 41.5% at 1, 2, and 3 years, respectively. CONCLUSIONS: Our study demonstrated that intravitreal injections of aflibercept initiated under a standardized T&E for patients with treatment-naïve nAMD allow for significant visual improvement at 12 months, which was maintained over a 3-year follow-up period.

Costs comparison of treating diabetic macular edema with aflibercept, ranibizumab or dexamethasone at 1 year in France (INVICOST study).

PURPOSE: INVICOST, a medico-economic analysis, compared costs of managing treatment-naive patients with diabetic macular edema (DME) receiving intravitreal injections (IVIs) of aflibercept (AFL), dexamethasone implant (DXI) or ranibizumab (RAN) over 1 year. METHODS: Healthcare resource use and associated costs were estimated using individual patient data from INVICTUS, a prospective, open-label, monocentric study. Healthcare costs comprised direct medical costs such as drug acquisition and administration, consultations and ophthalmological procedures. Costs were assessed from the French National Health Insurance perspective using published national tariffs expressed in 2019 euros. RESULTS: Of the 60 treated eyes, 48 had no treatment switch; 14 received AFL, 19 received DXI and 15 received RAN. AFL-treated eyes received an average of 6.5 IVIs, DXI-treated patients received 2 IVIs and RAN-treated received 6.8 IVIs. All treated eyes received an initial prescription for adjunctive ocular medications and 349 follow-up procedures were performed including an average of 3.9 optical coherence tomography and 3.2 retinography procedures per eye. Average total direct cost of per-eye treatment was €4516 (€1128-€8257). Average cost was €5782 for eyes treated with AFL, €2779 with DXI and €5536 with RAN. Drug therapy was the cost driver: €4394 (76%) for AFL, €1915 for DXI (69%) and €4268 (77%) for RAN. CONCLUSION: The difference in total treatment cost is largely explained by the significantly lower frequency of IVI and annual cost of therapy with DXI, compared with AFL and RAN. INVICOST is the first study comparing treatment costs with AFL, DXI and RAN in France in current clinical practice.

Evolution of Quantitative Optical Coherence Tomography Angiography Markers with Glycemic Control: A Pilot Study.

Aim: We aimed to analyze changes in retinal microvascularization with intensive reduction of glycated hemoglobin A1c (HbA1c) in patients with poorly controlled diabetes using quantitative optical coherence tomography angiography (OCT-A) metrics. Method: This was a retrospective observational study in patients with uncontrolled diabetes admitted to the hospital for glycemic control. A second set of 15 healthy volunteers was included to serve as a control group. OCT-A was performed at inclusion and at 3 months to measure foveal avascular zone area (FAZA), vessel density (VD) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP), acircularity index (AI), and fractal dimension (FD). Results: This analysis included 35 patients (35 eyes): 28 type-2 diabetics and 7 type-1 diabetics. Mean HbA1c was 13.1 ± 2.0% at inclusion and 7.0 ± 1.5% at 3 months. In the short period from inclusion to 3 months post-inclusion, patients showed significant decrease in VD−DCP (28.8% vs. 27.8%; p = 0.014), a significant increase in FAZA (0.300 mm2 vs. 0.310 mm2; p < 0.001), and a significant increase in AI (1.31 vs. 1.34; p < 0.01). Multivariate analysis found an increase in FAZA was correlated with baseline HbA1c level and age (R2 = 0.330), and a decrease in VD-DCP was correlated with HbA1c decrease and diabetes duration (R2 = 0.286). Conclusions: Rapid glycemic control in patients with uncontrolled diabetes led to possible short-term microvascular damage that correlated to both initial and decreased HbA1c.

INVICTUS: Intravitreal anti-VEGF and dexamethasone implant comparison for the treatment of diabetic macular edema: A 12 months follow-up study.

PURPOSE: To compare the efficacy of intravitreal injections (IVI) of ranibizumab (Lucentis®, Novartis, Basel, Switzerland; RAN), aflibercept (Eylea®, Bayer, Leverkusen, Germany; AFL) and dexamethasone implant (Ozurdex®, Allergan, Irvine, California; DXI) in the treatment of naive diabetic macular oedema (DME) during a 12-month follow-up, in real life. METHODS: Nineteen eyes treated with RAN, 20 with AFL and 21 with DXI were analysed from inclusion up to 12 months (M12) with intermediate analysis at M6. Best corrected visual acuity (BCVA), fundus and central retinal thickness (CRT) using spectral-domain optical coherence tomography (SD-OCT; Spectralis/HRA, Heidelberg Engineering, Germany) were performed at inclusion, M3, M6 and M12. RESULTS: BCVA improved until 67.9 letters ±13.3 SD (+5.5 letters) at M6 and 69.6 letters ±12 SD (+7.2 letters) at 12 months for RAN group (p = 0.036). For the AFL group it improved until 63.6 letters ±15.2 SD (+6.6 letters) at M6 and 67.5 letters ±12.2 SD (+8.5 letters) at 12 months (p = 0.014). Lastly DXI group improved by 66.9 letters ±15.1 SD (+7.9 letters) at M6 and 68.4 letters ±11.2 SD (+9.4 letters) at 12 months (p = 0.0023). CRT decreased by 124.4 µm at M6 and 99.3 µm at M12 in RAN group, 144.3 µm and 101.5 µm in AFL group and finally 95.6 µm and 162.7 µm in DXI group. CONCLUSION: In summary, these three drugs provide an efficient treatment option with an acceptable benefit-risk ratio for the treatment of naive patients with DME, whether on BCVA or CRT on the first year of treatment.

Multimodal Imaging Correlation of the Concentric Macular Rings Sign in Foveal Hypoplasia: A Distinctive Henle Fiber Layer Geometry.

PURPOSE: To expand the multimodal imaging correlation of the concentric macular rings (CMR) sign seen on ultra-widefield fundus photography in patients with foveal hypoplasia. DESIGN: Retrospective case series. PARTICIPANTS: Thirty-two patients with foveal hypoplasia who demonstrated the CMR sign on ultra-widefield fundus photography. METHODS: Inclusion criterion was the presence of a CMR sign detected on ultra-widefield fundus photography. MAIN OUTCOME MEASURES: Noninvasive multimodal retinal imaging, including ultra-widefield fundus photography, structural OCT, near-infrared reflectance, and blue fundus autofluorescence, were investigated. Horizontal dense B-scans and en face OCT images were acquired. RESULTS: Evaluation of all patients (n = 32 patients) demonstrated a CMR sign on ultra-widefield fundus photography. Structural OCT scans were consistent with foveal hypoplasia in all patients. En face OCT images acquired at the level of the Henle fiber layer highlighted similar concentric rings around the location of the incipient fovea. The series of concentric rings was not visible at any other level of the macula. A significant correlation was found between the horizontal diameter of the largest outer ring and foveal hypoplasia grades (P < 0.0001). CONCLUSIONS: The CMR sign seen on ultra-widefield fundus imaging may be a distinctive feature of foveal hypoplasia and can support this diagnosis, especially in patients in whom OCT cannot be performed (patients with poor fixation or nystagmus or young children). Multimodal imaging correlation suggests that these concentric rings occur exclusively at the level of the Henle fiber layer. This distinctive Henle fiber layer geometry may reflect an arrested development stage in the timeline of foveal maturation.

Covid-19-Associated Retinopathy: A Case Report.

A 53-year-old man presented with acute loss of vision, negative scotoma and dyschromatopsia in his left eye. He reported contact with people with severe respiratory syndrome - coronavirus-2 (SARS-CoV-2) 8 days prior symptoms. Funduscopic examination revealed several retinal hemorrhages. Spectral-domain optical coherence tomography showed lesions consistent with acute macular neuroretinopathy and paracentral acute middle maculopathy. Quickly after his presentation, SARSCov-2 was confirmed by chest computed tomography-scan and RT-PCR in this patient. Thrombotic complications associated with Covid-19 infection have high incidence and may involve the retina. We described a case of retinal involvement associated with Covid-19 infection. PRÉCIS: Funduscopic examination revealed retinal hemorrhages in a man with loss of vision. Optical coherence tomography showed an acute macular neuroretinopathy and paracentral acute middle maculopathy. Coronavirus disease was confirmed by chest computed tomography-scan and RT-PCR.

Persistent Placoid Maculopathy: Prognosis Factors and Functional Outcomes.

Purpose: To identify prognosis factors and functional outcomes of persistent placoid maculopathy (PPM). Methods: We collected personal PPM cases and combined them with the data from the literature. Results: 68 eyes of 37 patients with PPM were analyzed, including six new cases. Twenty-six patients were men (70%) with a mean age of 51.8 years old. The mean initial visual acuity (VA) was 0.52 LogMar ± 0.55 for a mean final VA of 0.49 LogMar ± 0.51. Risk factors for poor VA included: initial VA less than 0.2 LogMar (p < .0001), cardiovascular risk factor (p = .008), autoimmune-related and/or systemic pro-inflammatory conditions (p = .003), choroidal neovascularization (p = .001), macular atrophy (p = .03) and absence of systemic corticosteroid treatment (p = .03). Conclusion: PPM is a choroidal inflammation. Identifying prognosis factors may help to guide treatment and follow-up. We showed that anti-inflammatory drugs, and anti-VEGF injections in cases of choroidal neovascularization, may lead to better outcomes.

Diffuse subretinal fibrosis syndrome: A rare entity.

BACKGROUND/ PURPOSE:: Diffuse subretinal fibrosis and uveitis syndrome is an inflammatory disease rarely reported. The purpose of this article is to describe a rare case of diffuse subretinal fibrosis syndrome in an 8-year-old child. METHODS AND RESULTS:: The patient initially presented with a loss of vision in his right eye, with a visual acuity of 20/200. The visual acuity of the left eye was normal. Clinical examination showed bilateral anterior and posterior inflammation while the fundus revealed on the right eye an inter maculopapillar fibrosed lesion with a discrete retinal hemorrhage and a similar but smaller lesion on the left eye. The optical coherence tomography showed hyper-reflective material compatible with pre-retinal and subretinal pigment epithelial fibrosis and associated subretinal fluid. The angiography facilitated the diagnosis of neovascularization that was associated with the fibrotic lesion. The rest of the clinical pediatric examination remained negative and a diagnosis of diffuse subretinal fibrosis syndrome complicated with neovascularization was made. Treatment with systemic corticosteroids at the dose of 1 mg/kg/day for 1 month with a progressive decrease of 5 mg per month allowed for both anatomical and functional improvement. The visual acuity of the right eye improved from 20/200 to 20/63 at 1 month, 20/32 at 2 months, and 20/20 at 4 months. CONCLUSION:: To our knowledge, this is the first reported case of bilateral diffuse subretinal fibrosis complicated by neovascularization. General corticosteroid therapy proved to be effective in this case and appears to be a viable option in first-line treatment.

The Pattern of Recurrence in Diabetic Macular Edema Treated by Dexamethasone Implant: The PREDIAMEX Study.

PURPOSE: To assess the time to functional and anatomic recurrence of macular edema (ME) after a first intravitreal dexamethasone implant in eyes with diabetic macular edema (DME). DESIGN: A 6-month observational, prospective, uncontrolled, multicenter, national case series. PARTICIPANTS: Thirty-seven patients included between January 2015 and June 2016. METHODS: Patients were monitored at baseline and then monthly over 6 months after the first treatment. MAIN OUTCOME MEASURES: Different patterns of recurrence were defined: qualitative and quantitative anatomic recurrences and functional recurrence. RESULTS: Median ME duration before the first dexamethasone implant was 2.04 months. All patients received a dexamethasone implant for the first time, but 73% of patients had not undergone any form of treatment previously. The mean time from baseline to qualitative anatomic, quantitative anatomic, and functional recurrence was 4.22 months (95% confidence interval [CI], 3.80-4.65 months), 4.73 months (95% CI, 4.34-5.12 months), and 4.89 months (95% CI, 4.53-5.26 months), respectively. Almost all patients (7/8) who demonstrated a qualitative anatomic recurrence showed a subsequent quantitative anatomic and functional recurrence days later. Mean improvement in best-corrected visual acuity was 10.1 letters (95% CI, 6.7-13.4 letters) and 7.3 letters (95% CI, 4.1-10.6 letters) at months 2 and 6, respectively. The mean reduction in central subfield macular thickness was 206 µm (95% CI, 157-255 µm) and 146 µm (95% CI, 98-195 µm) at months 2 and 6, respectively. CONCLUSIONS: Dexamethasone implant is a functionally and anatomically effective treatment for DME in real-life practice. Qualitative anatomic recurrence seems to be an early sign of quantitative anatomic and functional recurrence. Further studies should demonstrate if early retreatment at the qualitative anatomic recurrence stage could better protect patient visual function.