An incipient late-onset retinal degeneration with a C1QTNF5 mutation: a case report with an 11-year follow-up.

PURPOSE: The purpose of this study was to describe and diagnose the difficulty in a long-term follow-up (eleven years) patient with a very early presentation of late-onset retinal degeneration (L-ORD) and the significance of electrophysiological examinations and follow-up in assessing undiagnosed inherited retinal diseases. METHODS: This is an observational case report of a 56-year-old woman, with scattered multiple yellow-white retinal dots firstly diagnosed as fundus albipunctatus. Ten years after presentation, a deterioration in rod and cone responses in ff-ERG was detected, which allowed us to discard the first diagnostic hypothesis and proceed with a genetic testing. RESULTS: Ten years after presentation, she presented a clear progression of the abnormal photoreceptor response with a cone and rod involvement in ff-ERG, which was not compatible with the previous suspicion of fundus albipunctatus. Six months later, genetic testing results together with the typical progression of atrophic patchy lesions in multimodal imaging allowed a certain diagnosis of L-ORD, caused by an already reported pathogenic variant in the C1QTNF5 gene (c.563C > T; p. Pro188 Leu). CONCLUSIONS: We demonstrate the importance of the ff-ERG examination and the follow-up (or ERG and imaging repetition) in the differential diagnosis of an incipient L-ORD, which can be easily misdiagnosed in the early stages, before the appearance of the characteristic chorioretinal atrophy seen with the progression of this rare disease.

SUBRETINAL TRANSIENT HYPOREFLECTIVITY IN AGE-RELATED MACULAR DEGENERATION: A Spectral Domain Optical Coherence Tomography Study.

PURPOSE: To describe and assess the prognostic significance of subretinal transient hyporeflectivity (STHR) on a novel spectral domain optical coherence tomography (SD-OCT) in age-related macular degeneration. METHODS: Consecutive patients with age-related macular degeneration (AMD) presenting STHR, defined as a small, well-defined, round subretinal, hyporeflective lesion, on SD-OCT and without exudative signs were included. Clinical examination and SD-OCT (SPECTRALIS, Heidelberg Engineering, Heidelberg, Germany) were analyzed at inclusion, 1 month before inclusion, and until the onset of exudative signs during the 12-month follow-up. RESULTS: Thirty-five STHR in 21 eyes of 20 patients were included. Among the 21 eyes, 2 eyes had early AMD, 1 eye had nonexudative asymptomatic macular neovascularization, and 18 eyes presented late AMD: 17 eyes neovascular AMD and 1 eye geographic atrophy. During the 2-month follow-up, 97.1% (34/35) of STHR disappeared. During the 12-month follow-up, 57.1% of eyes (12/21) developed exudative signs on 1 eye with early AMD and 11 eyes with neovascular AMD. CONCLUSION: Subretinal transient hyporeflectivity is a novel SD-OCT sign in patients with AMD. The eyes with isolated STHR should be closely monitored on a monthly basis to detect further exudation.

INTRAVITREAL RANIBIZUMAB FOR CHOROIDAL NEOVASCULARIZATION IN ANGIOID STREAKS: Four-Year Follow-up.

PURPOSE: To analyze retrospectively the efficacy of intravitreal ranibizumab injections for the management of choroidal neovascularization in patients with angioid streaks over a long term. METHODS: In this "nonrandomized," double-center, retrospective, interventional case series, a consecutive series of patients affected with choroidal neovascularization associated with angioid streaks were treated with intravitreal ranibizumab injections (0.5 mg/0.05 mL). Best-corrected visual acuity, fundus photography, optical coherence tomography, and fluorescein angiography were examined before and after treatment. The primary endpoint was the percentage of eyes with stable or improved visual acuity at the end of follow-up (loss of less than 3 Early Treatment Diabetic Retinopathy Study lines). Secondary endpoints were the percentage of eyes with stable or decreased macular thickness on optical coherence tomography (less than a 10% increase in macular thickness) and the percentage of eyes with persistent leakage on fluorescein angiography at the last observation carried forward. RESULTS: Thirty-five eyes of 27 patients were treated with repeated intravitreal ranibizumab injections (mean of 9.9 ± 7.2 injections, range 2-26) for a mean of 48.6 ± 17.1 months (range 8-66). At the end of follow-up, best-corrected visual acuity was stabilized or improved in 22 of 35 eyes (62.9%). Macular thickness had stabilized or decreased in 16 of 35 eyes (45.7%). At the last follow-up examination, on fluorescein angiography, no further leakage was observed in 27 of 35 eyes (77.1%). CONCLUSION: In this large series of patients with choroidal neovascularization associated with angioid streaks followed for 4 years, ranibizumab injections allowed stabilization of best-corrected visual acuity in most eyes. Ranibizumab appear as an effective therapeutic option in CNV associated with angioid streaks over long time.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FEATURES OF SUBRETINAL FIBROSIS IN AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To report the imaging features of subretinal fibrosis secondary to exudative age-related macular degeneration (AMD) on optical coherence tomography angiography. METHODS: All consecutive patients diagnosed with subretinal fibrosis complicating exudative AMD were imaged by color retinal photographs or multicolor imaging, fluorescein angiography, spectral domain optical coherence tomography, and optical coherence tomography angiography. Eyes with active exudative features observed during the last 6 months were compared with those without any sign of exudation >6 months. RESULTS: Forty-nine eyes of 47 consecutive patients were included. A blood flow inside the fibrotic scar could be detected in 46 of 49 cases (93.8%). Three patterns of vascular networks could be distinguished, that were described as pruned vascular tree (26 of 49 eyes; 53.1%), tangled network (14 of 49; 28.6%), and/or vascular loop (25 of 49; 51.0%). Furthermore, 2 types of hyporeflective structures, large flow void, and/or dark halo were observed in 63% and in 65% of eyes, respectively. The observed patterns did not differ between eyes with active or inactive lesions. CONCLUSION: Optical coherence tomography angiography of subretinal fibrosis showed almost constantly a perfused, abnormal vascular network and collateral architectural changes in the outer retina and the choriocapillaris layer. These features were associated with both active and inactive fibrotic choroidal neovessels.

TYPE 2 NEOVASCULARIZATION SECONDARY TO AGE-RELATED MACULAR DEGENERATION IMAGED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: Optical coherence tomography angiography is a novel and noninvasive technique for imaging retinal microvasculature by detecting changes in reflectivity that is related to blood flow. The purpose of this study was to describe Type 2 neovascularization characteristics in age-related macular degeneration using optical coherence tomography angiography. METHODS: Fourteen eyes of 14 consecutive patients with Type 2 neovascularization were prospectively included. All patients underwent a complete ophthalmological examination, including color and infrared fundus photography, fluorescein and indocyanine green angiography, spectral domain optical coherence tomography angiography, and optical coherence tomography angiography. RESULTS: In all cases, Type 2 lesions could be detected by optical coherence tomography angiography, presenting as a hyperflow lesion in the outer retina, with a glomerulus (4/14) or medusa shape (10/14), surrounded by a dark halo. The superficial layer and the deep retina showed no abnormal flow. Surprisingly, the Type 2 lesions could also be observed in the presumed choriocapillaris layer. These glomerulus- or medusa-shaped lesions were connected, in 10/14 eyes, to a thicker main branch, which seemed to continue deep into the choroidal layers. CONCLUSION: Optical coherence tomography angiography may be a new imaging method for the diagnosis of Type 2 neovascularization in clinical routine. However, the specificity of the features needs to be investigated in further studies.

Impact of reticular pseudodrusen on macular function.

PURPOSE: To investigate the impact of reticular pseudodrusen on macular function using microperimetry. METHODS: Eighteen consecutive patients (18 eyes) with reticular pseudodrusen (Group 1), and without medium/large drusen, underwent microperimetry. Eighteen age-matched and sex-matched subjects (18 eyes) with typical drusen and without pseudodrusen (Group 2) also underwent microperimetry. Macular sensitivity was assessed by microperimetry and compared between the two Groups. RESULTS: Mean age of patients with reticular pseudodrusen and with typical drusen was 77.3 ± 6.8 years and 75.0 ± 9.9 years, respectively (P = 0.4), and 61.1% and 61.1% were women, respectively. Mean best-corrected visual acuity was 0.14 ± 0.09 logarithm of the minimum angle of resolution and 0.13 ± 0.09 logarithm of the minimum angle of resolution (P = 0.8) in Group 1 and Group 2, respectively. Microperimetry revealed a significant difference in overall mean macular sensitivity ("square 7 × 7"; 49 points) between Group 1 and Group 2 (5.9 ± 1.7 dB vs. 8.8 ± 2.4 dB, P < 0.001). Both mean central macular sensitivity ("square 3 × 3"; 9 points) and mean peripheral macular microperimetric sensitivity (overall "square 7 × 7" - central "square 3 × 3"; 40 points) were significantly reduced in Group 1 compared with Group 2 (central macular sensitivity: 6.9 ± 1.7 dB vs. 8.9 ± 2.6 dB in Group 1 and Group 2, respectively; P = 0.01; peripheral macular sensitivity: 5.7 ± 1.8 dB vs. 8.7 ± 2.3 dB in Group 1 and Group 2, respectively; P < 0.001). In Group 1, mean peripheral sensitivity was reduced when compared with mean central sensitivity (5.7 ± 1.8 dB vs. 6.9 ± 1.7 dB, P = 0.01), whereas in Group 2, mean sensitivity was similar in both peripheral and central macula (8.7 ± 2.3 dB vs. 8.9 ± 2.6 dB, P = 0.4). CONCLUSION: Eyes with reticular pseudodrusen present a greater extent of reduced sensitivity than eyes with typical drusen.

Intravitreal dexamethasone implant (Ozurdex) for macular edema secondary to retinitis pigmentosa.

BACKGROUND: To evaluate the anatomical and functional outcomes of intravitreal dexamethasone implant in patients with macular edema (ME) secondary to retinitis pigmentosa (RP). METHODS: Three patients (four eyes), aged 24 to 46 years, presented with refractory ME secondary to RP. Intravitreal dexamethasone implant (Ozurdex) was administered to treat ME. The anatomical (central macular thickness [CMT]) and functional (best-corrected visual acuity [BCVA]) outcomes as well as adverse events were recorded. RESULTS: All patients completed 6 months follow-up. After intravitreal Ozurdex all patients showed regression of ME. At baseline, mean CMT was 443 ± 185 µm (range 213-619 µm); ME improved to 234 ± 68 µm (range 142-307 µm) at 1 month, to 332 ± 177 µm (range 139-513 µm) at 3 months, and to 305 ± 124 µm (range 144-447 µm) at 6 months. Recurrent ME was recorded in 2 patients (both patients at 3 months from intravitreal dexamethasone implant). Retreatment with intravitreal Ozurdex was performed in two patients. Mean BCVA improved form 20/160 (range 20/50-20/200) (baseline) to 20/100 (range 20/40-20/125) at 1 month, to ∼20/125 (range 20/100-20/200) at 3 months, and to ∼ 20/125 (range 20/100-20/160) at 6 months. No serious ocular and systemic adverse events were observed during the study period. CONCLUSIONS: Intravitreal dexamethasone implant provides anatomic and functional improvements and may represent a valuable treatment option for patients with ME secondary to RP.

Management of diabetic macular oedema in France from 2012 to 2018: The nationwide LANDSCAPE study.

OBJECTIVE: To describe the management of diabetic macular oedema (DME) patients from the entire French population between 2012 and 2018. METHODS: In this retrospective longitudinal study, we identified adults treated for DME from the French population using the exhaustive French National Health Information database (SNDS), and an algorithm based on diagnosis and procedure codes, and reimbursed treatments. RESULTS: Between 2012 and 2018, we identified 53 584 treated DME patients, who were followed for up to 7 years from DME treatment initiation. Optical coherence tomography (OCT) became the predominant imaging tool to diagnose DME. Only 14% of patients consulted a diabetologist or endocrinologist in the 3 months prior to initiating DME treatment, whereas 84% consulted a general practitioner. The percentage of patients consulting an ophthalmologist declined over time, from 97% of patients in Year 1 (median of 9 consultations), to 46% in Year 7 (median of 7 consultations). The median DME treatment duration with an anti-VEGF and/or dexamethasone implant treatment was 9 months; 54% of patients had a treatment duration less than 1 year. First-line treatment was more common with ranibizumab (55% of patients) than with aflibercept (30%), or dexamethasone implant (15%). About 25% of patients who initiated anti-VEGF treatment switched treatment at least once, while 30% of patients who initiated dexamethasone implant switched to anti-VEGF treatment at least once. CONCLUSIONS: French DME patients seem well-monitored by their ophthalmologist, but median DME treatment duration was just 9 months. These results emphasise the challenge to manage and treat patients with DME over the long term.

Management of Neovascular Age-Related Macular Degeneration Treatment in France from 2008-2018: The Nationwide LANDSCAPE Study.

INTRODUCTION: The aim of this study was to describe the management of neovascular age-related macular degeneration (nAMD) in French patients between 2008 and 2018. METHODS: This was a retrospective longitudinal cohort study using exhaustive nationwide health records from the French National Health Information database. Enrollment criteria were adults aged ≥ 50 years, nAMD diagnosis, or reimbursement for nAMD treatments (anti-vascular epithelial growth factor [VEGF] injection or dynamic phototherapy with verteporfin). Exclusion criteria were high myopia, diagnosis of other retinal diseases, and treatments for other macular diseases (dexamethasone implant, laser). Main outcome measures were consumption of medical care and nAMD treatments per calendar year and number of years of follow-up. RESULTS: Between 2008 and 2018, we identified 342,961 patients who have been treated for nAMD. Median duration of ophthalmological follow-up exceeded 7 years (90 months). The median annual number of ophthalmology consultations decreased from nine visits in year 1 after treatment initiation to four visits from year 7 onwards. The median duration of nAMD treatment was 10.1 months for all patients, with 48.5% of patients undergoing treatment for < 1 year. Only 24.4% of patients had maintained treatment at year 11. Patients remaining under treatment had a median of four anti-VEGF treatments per year throughout the 10-year study period. Ranibizumab was the more common first-line treatment (67.5% of patients) compared to aflibercept (32.4%). About 20% of patients who initiated treatment switched treatment at least once. CONCLUSIONS: LANDSCAPE provides exhaustive nationwide data on the real-world management of nAMD in France over a 10-year period. Further investigation into short treatment duration is required, especially in terms of understanding its relation to visual outcomes.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IMAGING OF CHOROIDAL NEOVASCULARIZATION SECONDARY TO CHOROIDAL RUPTURE TREATED BY INTRAVITREAL RANIBIZUMAB.

PURPOSE: To describe optical coherence tomography angiography findings at baseline and during the follow-up of choroidal neovascularization secondary to choroidal rupture (CR) in a patient with kidney transplant treated by a single intravitreal injection of ranibizumab. METHODS: The clinical course, conventional multimodal imaging findings including ultra-widefield fundus color photography and fundus autofluorescence (Optos California, Marlborough, MA), spectral-domain optical coherence tomography (SD-OCT Spectralis; Heidelberg Engineering, Heidelberg, Germany), fluorescein angiography (FA; Heidelberg Engineering, Heidelberg, Germany), indocyanine green angiography ,and optical coherence tomography angiography (Plex-Elite, Carl Zeiss Meditec, Inc, Dublin, CA) findings at baseline and during the follow-up of a patient with choroidal neovascularization secondary to CR. RESULTS: A 19-year-old young man with a history of blunt trauma presented with acute visual decline of the right eye. He had a systemic history of kidney transplant. His best-corrected visual acuity was 20/200 in the right eye and 20/20 in the left eye at baseline. Funduscopic examination and ultra-widefield fundus autofluorescence imaging revealed a double vertical macular lesion corresponding to a CR in the right eye. Spectral-domain optical coherence tomography, fluorescein angiography, and indocyanine green angiography revealed active Type 2 choroidal neovascularization secondary to the CR. Optical coherence tomography angiography showed a high-flow neovascular network consistent with conventional multimodal imaging. One month after intravitreal injection of ranibizumab, bestcorrected visual acuity was 20/100, optical coherence tomography angiography showed a contraction and remodeling of the neovascular flow, and exudative signs disappeared on multimodal imaging. No side effect was detected. CONCLUSION: Optical coherence tomography angiography is able to detect choroidal neovascularization secondary to CR at baseline and during the follow-up after a single intravitreal injection of ranibizumab. Ranibizumab was effective in the treatment of this sight-threatening lesion in a patient with a history of kidney transplant.