A case of recurring acute exudative polymorphous vitelliform maculopathy successfully treated with intravitreal Ozurdex injection.

INTRODUCTION: We describe a case of acute exudative polymorphous vitelliform maculopathy (AEPVM) that recurred 9 years after the initial event. To the best of our knowledge, this is the first report of recurrent AEPVM showing recovery of retinal and retinal pigment epithelium (RPE) function and good visual outcome following treatment with intravitreal corticosteroid. CASE DESCRIPTION: A 45-year-old Caucasian woman first presented with AEVPM in 2009. Her condition spontaneously resolved and she remained stable over several years. 9 years later, her condition recurred with bilateral reduction in visual acuity. Fundus examination revealed multiple small yellowish subretinal lesions across the posterior pole in both eyes. Optical coherence tomography (OCT) showed bilateral cystoid macular oedema (CMO). She was referred for electrophysiology and her electrooculogram findings were in keeping with severe generalised RPE dysfunction bilaterally, with a light peak to dark trough ratio (Arden index) of 110%, comparable to her initial presentation 9 years earlier. She was initially treated with oral steroids with some improvement. However, the maculopathy in the left eye recurred on cessation of oral treatment. A sustained-release 700ug dexamethasone intravitreal implant (Ozurdex®) was inserted in the left eye to which she responded remarkably, with improvement in visual acuity and complete resolution of the CMO. A year later, at her most recent clinic visit in March 2021, there was no evidence of any further recurrence. CONCLUSION: Our case demonstrates clinical and imaging findings consistent with recurrence of AEPVM with CMO that has been successfully treated with Ozurdex®.

Choroidal neovascularization associated with butterfly-shaped pattern dystrophy - a case report.

The pattern dystrophies (PDs) are a group of primarily autosomal dominant inherited macular diseases that cause the deposition of lipofuscin in retinal pigment epithelium (RPE) and may lead to significant vision loss in later life. Patients can develop choroidal neovascularization (CNV) and/ or geographic atrophy (GA) and for this reason they are often misdiagnosed as age-related macular degeneration (AMD). We presented a case of a 66-year-old patient complaining of vision loss in the right eye (RE) for 8 months. At the initial examination, his best corrected visual acuity (BCVA) was 0.6 in the RE. Optical coherence tomography angiography (OCTA), fundus autofluorescence (FAF) and fundus fluorescein angiography (FFA) allowed to diagnose butterfly-shaped PD in both eyes with choroidal neovascularization (CNV) in the RE. The patient was treated with three intravitreal anti-vascular epithelial growth factor (anti-VEGF, ranibizumab) injections during six weeks intervals, which improved and stabilized the BCVA of the RE to 0.7 during the over two-year observation period. Our report contributes to the still limited data regarding CNV associated with butterfly-shaped PDs and the results of treatment with ranibizumab. Abbreviations: AMD = age-related macular degeneration, anti-VEGF = anti-vascular epithelial growth factor, AOFVD = adult-onset foveomacular vitelliform dystrophy, BCVA = best corrected visual acuity, CNV = choroidal neovascularization, FAF = fundus autofluorescence, FFA = fundus fluorescein angiography, GA = geographic atrophy, LE = left eye, MIDD = maternally inherited diabetes and deafness, OCT = optical coherence tomography, OCTA = optical coherence tomography angiography, OU = oculus uterque, both eyes, PD = pattern dystrophy, PDSFF = pattern dystrophy simulating fundus flavimaculatus, PDT = photodynamic therapy, PRPH2 = peripherine-2, RE = right eye, RPE = retinal pigment epithelium, VA = visual acuity.

Optical coherence tomography angiography cyclic remodeling of CNV in patients affected by Best macular dystrophy.

PURPOSE: To evaluate the effect of photodynamic therapy and/or intravitreal injections on choroidal neovascularization in treatment-naïve patients affected by Best Macular Dystrophy using OCT-A. MATERIALS AND METHODS: BMD patients with CNV treated using PDT and/or IV were included in the study. All patients underwent a complete ophthalmological examination, OCT and 3 × 3 mm OCT-A. The OCT-A images were analyzed using an open-source software (ImageJ) to assess the CNV membrane area (CNV-MA), the CNV vessel area (CNV-VA), and vessel density (VD) at the follow-ups (3 months after PDT and 1 month after IV). RESULTS: Five eyes of four patients with CNV were included. All eyes received PDT as first-line therapy; 4 eyes underwent more than 1 treatment session: three eyes received 1 IV, whereas one eye had one further PDT. After PDT, the CNV-MA, CNV-VA, and VD quantitative parameters were obtained for four out of five eyes: in three eyes of two patients CNV-MA, CNV-VA, and VD first decreased and then gradually increased during follow-up, whereas in one eye of one patient CNV-MA, CNV-VA, and VD slightly increased. After IV the CNV-MA, CNV-VA, and VD had significantly decreased at the 1-month follow-up in three eyes of three patients. CONCLUSION: OCT-A is an important tool for the diagnosis of both naïve and fibrotic CNV in BMD patients; it is a non-invasive method for the qualitative and quantitative analysis of neovascular lesions during follow-up. Our results have shown a cyclic remodeling of treated CNV in BMD patients using both PDT and IV.

Anti-VEGF and Retinal Dystrophies.

The therapeutic approach based on anti-vascular endothelial growth factor (anti-VEGF) molecules can be used to treat two important complications of retinal dystrophies: choroidal neovascularization and macular edema. The macular involvement in retinal dystrophies can lead to further visual deterioration in patients at a young age and already affected by functional limitations. The study reports the effect of anti-VEGF treatment in several subforms of retinal dystrophies, critically discussing advantages and limitations.

SEROUS MACULAR DETACHMENT IN BEST DISEASE: A Masquerade Syndrome.

PURPOSE: To describe the clinical and multimodal imaging findings of a series of cases of serous macular detachment (SMD) caused by Best disease (BD) masquerading as neovascular age-related macular degeneration or central serous chorioretinopathy that were inappropriately treated with intravitreal anti-vascular endothelial growth factor or laser therapy. This study will also present data to support age-related progressive choroidal thickening in BD patients, which may play a role in the development of SMD in this population. METHODS: Clinical examination and multimodal imaging findings, including color fundus photography, spectral-domain optical coherence tomography, fundus autofluorescence, fluorescein angiography, and optical coherence tomography-angiography, were reviewed and analyzed. Subfoveal choroidal thickness was also formally measured, and an age-related choroidal thickness analysis was performed and compared with a normal population. RESULTS: Twenty-six eyes of 13 patients (5 women) were included. Median age was 44 years. Nine patients presented with a history of SMD and subretinal fluid recalcitrant to various therapies, including intravitreal anti-vascular endothelial growth factor injections and photodynamic therapy. Best disease was subsequently diagnosed genetically in six patients and by detailed family history in seven. Mean logarithm of the minimum angle of resolution best-corrected visual acuity for all 26 eyes at last follow-up was +0.36 (Snellen equivalent of 20/46). Subfoveal choroidal thickness positively correlated with age for our cohort, increasing linearly at a rate of 25.6 µm per decade (R = 0.64; P < 0.001). Choroidal neovascularization was identified in four eyes on optical coherence tomography angiography, but these eyes did not respond to anti-vascular endothelial growth factor treatment. CONCLUSION: The diagnosis of BD should be considered in patients presenting with SMD and recalcitrant subretinal fluid masquerading as neovascular age-related macular degeneration or chronic central serous chorioretinopathy to avoid unnecessary treatment procedures. The positive correlation of subfoveal choroidal thickness with age in BD patients may be a factor in the pathogenesis and development of SMD in this population. Recognizing the multimodal imaging features of SMD associated with BD, described in detail in this study, will guide practitioners to the accurate diagnosis of BD and reduce the risk of unnecessary intraocular procedures with potential complications.

Treatment of Macular Degeneration with Sildenafil: Results of a Two-Year Trial.

OBJECTIVE: To evaluate PDE5/6 inhibition with sildenafil to reduce choroidal ischemia and treat age-related macular degeneration. METHODS: Sildenafil was prescribed to treat participants with macular degenerations or macular dystrophies measured by spectral-domain optical coherence tomography, color fundus photography, enhanced depth imaging, and best-corrected visual acuity. RESULTS: No change in calcified drusen was noted. Vitelliform-type soft drusen were not substantially changed. A participant with Best vitelliform macular dystrophy had a significant improvement in vision as well as in photoreceptor and ellipsoid layers. CONCLUSIONS: Our research supports sildenafil as a safe treatment for age-related and vitelliform macular degenerations. Thickened Bruch's membrane reduces the beneficial effect of perfusion increase, but all eyes appear to benefit from PDE6. Notably, maintenance or improvement in the photoreceptor layer may be the most significant result of sildenafil and is consistent with PDE6 inhibition. Thus, sil-denafil treatment of macular degeneration offers significant potential for vision retention and recovery.

Acute Exudative Polymorphous Vitelliform Maculopathy Syndrome; natural history and evolution of fundal and OCT images over time.

A 33-year-old man presented with a 10-day history of bilateral blurred vision on a background of a prodromal influenza-like illness. Ocular Coherence Tomography (OCT) and fundal examination coincided with a diagnosis of atypical central serous retinopathy. The patient's symptoms worsened during follow-up, and he was started on steroids. Subsequent fundal examination revealed yellow deposits in a honeycomb pattern and hard exudates in the perimacular region. Serial OCTs revealed progression of bilateral macular intraretinal and subretinal fluid. He was subsequently admitted to hospital for a full paraneoplastic workup. Liaison with our colleagues in other specialist retinal centres led us to a diagnosis of acute exudative polymorphous vitelliform maculopathy syndrome. We subsequently took fundal images to monitor disease progression and to monitor changes seen with autofluorescence in this rare disease entity.

Acute Exudative Polymorphous Paraneoplastic Vitelliform Maculopathy Managed With Intravitreal Aflibercept.

The authors report on two patients with bilateral acute exudative polymorphous paraneoplastic vitelliform maculopathy (AEPPVM) treated with intravitreal aflibercept (Eylea; Regeneron, Tarrytown, NY [marketed locally in Turkey by Bayer]). Underlying malignancy had been treated in each case, including breast carcinoma in one case and colon carcinoma in the other case. A macular vitelliform lesion was noted in the right eye and atrophic retinal pigment epithelial (RPE) changes were noted in the left eye of each case. Enhanced depth imaging optical coherence tomography (EDI-OCT) of the vitelliform lesion showed sensorineural retinal detachment, highly reflective subretinal material, ellipsoid loss in the right eye, and photoreceptor loss in both eyes of each patient. In both cases, the right eye with a vitelliform macular lesion was treated with intravitreal aflibercept (2.0 mg/0.05 mL) at monthly intervals for the first three injections and at bimonthly intervals for the following injections. Case 1 received a total of six injections and visual acuity (VA) increased from 20/70 to 20/50 at 10 months' follow-up. EDI-OCT showed slight gradual resolution of subretinal vitelliform material. Case 2 received three injections and VA increased from 20/100 to 20/40 at 4 months' follow-up with a decrease in the subretinal vitelliform deposit and intraretinal edema on EDI-OCT. Intravitreal aflibercept may control progression of APPVME in newly diagnosed cases by decreasing vascular leakage and stabilizing RPE function. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:844-850.].

Retinal structure in young patients aged 10 years or less with Best vitelliform macular dystrophy.

PURPOSE: Our aim was to analyze retinal structure in young patients with Best disease with reference to future gene therapy. METHODS: This was a retrospective observational spectral domain optical coherence tomography study of four patients aged 10 years or less with Best disease. RESULTS: Findings ranged from subtle thickening at the level of the retinal pigment epithelium-photoreceptor interdigitation line, to subretinal fluid and precipitate-like changes at the level of the photoreceptor outer segments, and further to choroidal neovascularization. The photoreceptor inner segment ellipsoid layer could be visualized seemingly undisturbed above the vitelliform lesions, except in the case of choroidal neovascularization. CONCLUSIONS: Clinical variability is evident even among young patients aged 10 years or less with Best disease. The earliest structural alterations seem to occur at the level of the retinal pigment epithelium-photoreceptor interdigitation line. The photoreceptor inner segment seems to be unaffected unless choroidal neovascularization develops, which seems promising regarding future gene therapy.

Pharmacological Modulation of Photoreceptor Outer Segment Degradation in a Human iPS Cell Model of Inherited Macular Degeneration.

Degradation of photoreceptor outer segments (POS) by retinal pigment epithelium (RPE) is essential for vision, and studies have implicated altered POS processing in the pathogenesis of some retinal degenerative diseases. Consistent with this concept, a recently established hiPSC-RPE model of inherited macular degeneration, Best disease (BD), displayed reduced rates of POS breakdown. Herein we utilized this model to determine (i) if disturbances in protein degradation pathways are associated with delayed POS digestion and (ii) whether such defect(s) can be pharmacologically targeted. We found that BD hiPSC-RPE cultures possessed increased protein oxidation, decreased free-ubiquitin levels, and altered rates of exosome secretion, consistent with altered POS processing. Application of valproic acid (VPA) with or without rapamycin increased rates of POS degradation in our model, whereas application of bafilomycin-A1 decreased such rates. Importantly, the negative effect of bafilomycin-A1 could be fully reversed by VPA. The utility of hiPSC-RPE for VPA testing was further evident following examination of its efficacy and metabolism in a complementary canine disease model. Our findings suggest that disturbances in protein degradation pathways contribute to the POS processing defect observed in BD hiPSC-RPE, which can be manipulated pharmacologically. These results have therapeutic implications for BD and perhaps other maculopathies.

Intravitreal dexamethasone implant for acute exudative polymorphous vitelliform maculopathy.

PURPOSE: Acute exudative polymorphous vitelliform maculopathy is a rare retinal disease characterized by bilateral serous macular detachment and subretinal accumulation of yellowish deposits resembling Best dystrophy lesions. Corticosteroid systemic therapy has been used empirically in the attempt to treat this retinal disorder with mixed results. Thus, the benefit of corticosteroid remains undetermined. To our knowledge, we report the first case of acute exudative polymorphous vitelliform maculopathy (AEPVM) treated in one eye with intravitreal dexamethasone implant (Ozurdex; Allergan, Inc., Irvine, California, USA). METHODS: A 28-year-old man with AEPVM underwent intravitreal dexamethasone implantation in the left eye. RESULTS: Compared with the fellow eye, intravitreal dexamethasone implant did not significantly modify the clinical course of the disease. No implant-related complication was experienced during follow-up. CONCLUSIONS: The lack of response to intravitreal dexamethasone seems to suggest that corticosteroids may be ineffective for the treatment of AEPVM.

Bevacizumab treatment for choroidal neovascularization associated with adult-onset foveomacular vitelliform dystrophy.

PURPOSE: To evaluate choroidal neovascularization (CNV) associated with adult-onset foveomacular vitelliform dystrophy (AOFVD) and its response to bevacizumab therapy. METHODS: Demographics, clinical characteristics, response to bevacizumab therapy, and central foveal thickness (CFT) were retrospectively assessed in 11 eyes with CNV associated with AOFVD. Sixty consecutive patients with neovascular age-related macular degeneration (AMD) were compared to the patients with AOFVD for all clinical characteristics and responses evaluated. RESULTS: The mean (±SD) initial logMAR visual acuity (0.7 ± 0.8 vs. 1 ± 0.75), age at onset, number of bevacizumab injections (12.4 ± 10.4 vs 9 ± 6.7), and final logMAR visual acuity (0.87 ± 0.7 vs 1 ± 0.85) were similar between AOFVD and AMD. The mean CFT in AOFVD was reduced from 418 ± 144 µm to 330 ± 64 µm following treatment (p = 0.03). At the final examination, visual acuity had improved in 3 eyes, stabilized in 1 eye, and was reduced in 7 of the AOFVD eyes examined. CONCLUSIONS: Bevacizumab therapy for AOFVD-associated CNV resulted in reduced foveal thickness, but a guarded visual outcome was still found, due to progression of the vitelliform lesions.

A case of neurosyphilis revealed by acute exudative polymorphous vitelliform maculopathy.

The authors report the case of a healthy 56-year-old man presenting with bilateral vision loss. Clinical features were consistent with the diagnosis of acute exudative polymorphous vitelliform maculopathy (AEPVM). The patient returned 10 days later with bilateral anterior granulomatous uveitis, and the inflammatory work-up revealed treponemal antibodies in the serum and spinal fluid, consistent with a diagnosis of active neurosyphilis. The patient received standard treatment for neurosyphilis with intravenous penicillin G. Two months later, the intraocular inflammation had resolved, but the resolution of the vitelliform lesions was more gradual. An immune process could be a plausible explanation for these clinical findings. Clinicians should be aware that syphilis can produce AEPVM.

Desprendimiento viteliforme adquirido en paciente con drusas cuticulares tratado con bevacizumab / Bevacizumab treatment for acquired vitelliform detachment in patient with cuticular drusen

Caso clínico: Varón de 30 años, diagnosticado de desprendimiento viteliforme adquirido (DVA) secundario a drusas cuticulares que presentaba metamorfopsias en su OD. Se trató con inyecciones intravítreas de bevacizumab (Avastin), respondiendo favorablemente. Discusión: Enfermedad independiente, de fenotipo genético aún desconocido, debida a una disfunción generalizada del epitelio pigmentario retiniano (EPR). Evoluciona en un 50% a DVA; con la ayuda de nuevas pruebas complementarias llegamos a un diagnóstico certero. Sin tratamiento efectivo hasta el momento. Dada la frecuencia con la que se desarrolla neovascularización coroidea (NVC), creemos que el tratamiento con fármacos anti-VEGF podría ayudarnos en la estabilización o mejoría funcional y/o anatómica del cuadro (AU)

Case report: We report a case of a 30-year-old male with acquired vitelliform detachment (AVD) secondary to cuticular drusen and suffering from metamorphopsia in his right eye. Intravitreal bevacizumab (Avastin) was administered, achieving successful results. Discussion: An independent disease, of unknown genetic phenotype, caused by a generalized dysfunction of the retinal pigment epithelium (RPE). About 50% of patients develop AVD, and a correct diagnosis can be made with the help of new complementary tests. With no effective treatment currently available, and because of the incidence of developing choroidal neovascularization (NVC), treatment with anti-VEGF could help stabilize or improve the disease functionally and/or anatomically (AU)

Clinical findings of acquired vitelliform lesions associated with retinal pigment epithelial detachments.

PURPOSE: To study clinical findings associated with acquired vitelliform lesions in retinal pigment epithelial detachments (PEDs). DESIGN: Retrospective, interventional, consecutive case series. METHODS: We retrospectively reviewed 32 eyes of 24 patients (22 men, 2 women; age range [mean], 58-85 [73.7] years) with acquired vitelliform lesions. RESULTS: All eyes had acquired vitelliform lesions in the central macula associated with a serous PED at baseline. Of the 32 eyes, 30 (93.8%) were observed for 12 months, 26 (81.3%) for 24 months, and 17 (53.1%) for 36 months. The mean logarithm of the minimal angle of resolution best-corrected visual acuity (BCVA) levels were 0.19 at month 12, 0.28 at month 24, and 0.25 at month 36, none of which differed significantly from baseline. The mean changes in the BCVA were declines of 0.38, 1.29, and 1.21 lines at months 12, 24, and 36, respectively. Of 7 eyes treated with 3 consecutive monthly intravitreal injections of ranibizumab, the serous PEDs remained in all 7 eyes and the mean changes of BCVA were a decline of 2.40 lines 12 months after the first injection and a decline of 3.58 lines at the final visit. In the 24 untreated eyes, the mean change in the BCVA was a decline of 0.25 line at the final visit, which differed significantly (P = .021) compared with that of the treated eyes at the final visit. CONCLUSION: Intravitreal injections of ranibizumab were ineffective because of the absence of resolution of the PEDs and the declines in VA.

Ranibizumab for choroidal neovascularization associated with adult-onset foveomacular vitelliform dystrophy: one-year results.

PURPOSE: To evaluate the efficacy of intravitreal injections of ranibizumab for choroidal neovascularization associated with adult-onset foveomacular vitelliform dystrophy. METHODS: Retrospective case series of 24 eyes affected with choroidal neovascularization associated with adult-onset foveomacular vitelliform dystrophy treated by intravitreal injections of ranibizumab (0.5 mg/0.05 mL). Best-corrected visual acuity, fundus examination, spectral domain optical coherence tomography, fundus autofluorescence, and fluorescein and indocyanine green angiography were performed for the diagnosis of adult-onset foveomacular vitelliform dystrophy and choroidal neovascularization. After initial 3 monthly injections of ranibizumab, patients were followed up monthly and retreated if neovascular activity persisted. Outcome measure was the proportion of patients losing fewer than 3 lines of visual acuity from baseline to 12 months (final visit). RESULTS: At final visit, the mean number of ranibizumab injections was 4.5 ± 1.29. From baseline to final visit, 21 of 24 eyes (87.5%) lost fewer than 3 lines of visual acuity. Mean best-corrected visual acuity did not change significantly from baseline to final visit (0.37 ± 0.2 logarithm of the minimum angle of resolution vs. 0.30 ± 0.25 logarithm of the minimum angle of resolution, respectively; P = 0.115). Mean central macular thickness significantly decreased from baseline to final visit (327 ± 83 µm vs. 260 ± 57 µm, respectively; P = 0.001). CONCLUSION: In this series, ranibizumab succeeded in stabilizing best-corrected visual acuity in patients with choroidal neovascularization associated with adult-onset foveomacular vitelliform dystrophy. Ranibizumab seems to be a reasonable therapeutic option in this condition.

An evidence-based review of vascular endothelial growth factor inhibition in pediatric retinal diseases: part 2. Coats' disease, best disease, and uveitis with childhood neovascularization.

Vascular endothelial growth factor (VEGF) is an important factor in the pathogenesis of multiple retinal neovascular disorders. This report focuses on the quality and depth of new evidence for the use of VEGF inhibitors in selected pediatric ocular diseases, including Coats' disease, Best disease, and childhood uveitis. Because much of the literature comprises case reports and retrospective case series, the level of evidence supporting its use as a primary treatment option, or even as adjuvant therapy, is low. The standard of care is treatment of the underlying disorder to prevent neovascularization (retinal or subretinal), vitreous hemorrhage, or subsequent retinal detachment. However, these complications may not present until late in the disease course. It may then be useful to treat with these agents. Prospective studies are warranted to further elucidate the role of anti-VEGF therapy in these diseases.

Intravitreal ranibizumab for type 3 choroidal neovascularization complicating adult onset foveomacular vitelliform dystrophy.

PURPOSE: To describe the results obtained with intravitreal ranibizumab injections in a patient with adult onset foveomacular vitelliform dystrophy (AOFVD) complicated by Type 3 choroidal neovascularization (CNV). METHODS: A 78-year old man diagnosed with AOFVD presented at our department for decreased vision in his left eye (LE) (20/80). Upon a complete ophthalmologic examination, including fluorescein angiography, indocyanine green angiography, and spectral-domain optical coherence tomography, the patient was diagnosed with Type 3 CNV. Three monthly injections of ranibizumab 0.05 ml/0.5mg were administered intravitreally without complications. RESULTS: After the first injection, visual acuity of the LE improved (20/64) and regression of the Type 3 CNV was observed by fluorescein angiography, indocyanine green angiography and OCT. Six months after the final ranibizumab injection, a more-or-less complete resolution of the exudative retinal changes was observed. CONCLUSIONS: Type 3 CNV may be associated with AOFVD. Intravitreal ranibizumab may represent a possible therapeutic option in this unusual context.

Functional and anatomic changes in bilateral choroidal neovascularization associated with vitelliform macular dystrophy after intravitreal bevacizumab.

PURPOSE: We report the case of a young man with choroidal neovascularization (CNV) associated with vitelliform macular dystrophy (Best's disease), who underwent treatment with intravitreal bevacizumab. CASE: A 17-year-old white male presented for a routine ocular examination after reduction of visual acuity and was diagnosed with CNV in both eyes secondary to Best's disease. The diagnosis was confirmed by an ophthalmologic examination that included fluorescein angiography, indocyanine green angiography, Fourier optical coherence tomography, and microperimetry. Best corrected visual acuity was 5/10 in the right eye and 6/10 in the left eye. An intravitreal injection of bevacizumab was administered in both eyes. RESULTS: One month after bevacizumab injection, vision was 10/10 in both eyes. At a follow-up of 18 months, there was an absence of the neovascularization activity, and microperimetry revealed a marked improvement in retinal macular sensitivity. CONCLUSION: Intravitreal bevacizumab injection induced total regression of CNV as well as a morphologic and functional improvement in a young man affected by bilateral CNV secondary to Best's disease in a long-term follow-up.