Lack of Response to Intravitreal Ranibizumab Treatment in Adult Onset Foveomacular Vitelliform Dystrophy Complicated with Choroidal Neovascularization: A Case Report

Adult-onset foveomacular vitelliform dystrophy (AOFVD) is a rare disease characterized by accumulation of yellowish deposits in the macula. Rarely, it may be complicated by choroidal neovascularization (CNV). Cases with CNV may be confused with occult CNV in age-related macular degeneration. In our case, we will present the visual and anatomical results of a patient with AOVF-related CNV, in which we administered 3 doses of intravitreal ranibizumab (IVR). A 59-year-old female patient, who attended our clinic with the complaint of decreased vision in both eyes, was diagnosed with AOVF-related CNV in both eyes and was treated with 3 doses of IVR for 3 months. Despite the improvement in visual and anatomical functions 1 month after the first dose, vision decreased, and anatomical functions regressed to the pre-injection state in continued injections. IVR therapy is not an appropriate treatment option in the treatment of AOVF-associated CNV.

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®.

Quantitative microvascular alterations in butterfly-shaped pattern dystrophy and adult-onset foveomacular vitelliform dystrophy.

PURPOSE: To study retinal microvascular parameters in patients with butterfly-shaped pattern dystrophy (BPD) and adult foveomacular vitelliform dystrophy (AFVD). METHODS: This case-control study included BPD and AFVD patients in a tertiary university hospital. Eyes with known ocular disease and prior ocular surgery other than uncomplicated cataract surgery were excluded. Right eyes of healthy individuals without systemic or ocular disease were included as controls. En face 6×6mm angiograms were obtained with the RTVue XR Avanti (Optovue, USA). We used the Kruskal-Wallis test to compare vessel density (VD) values of the retina, optic disc and foveal avascular zone (FAZ) between groups. Dunn-Bonferroni correction was used for pairwise comparisons. RESULTS: Eighteen eyes of 10 BPD patients, 17 eyes of 9 AFVD patients, and 26 right eyes of 26 controls were included. Six patients in the BPD, 4 patients in the AFVD, and 16 patients in the control group were female. The groups did not differ by sex (P=0.650). AFVD patients were of higher mean age (64.3±7.8) than BPD patients (55.9±11.1) and controls (53.6±5.5) (P=0.008, p=0.009). In BPD (P=0.008, P=0.044) and AFVD (P=0.006, P=0.002), parafoveal and perifoveal vessel density (VD) of the superficial capillary plexus were lower than controls. Parafoveal VD of the deep capillary plexus in AFVD was lower than in controls (P=0.012). There was no difference in the foveal avascular area between groups (P=0.563). Optic discs parameters did not differ. CONCLUSION: A comparable loss in vascular density may indicate shared pathophysiology or represent a common sign of impairment in retinal homeostasis. Further research is needed to clarify underlying microvascular pathogenetic mechanisms in pattern dystrophies.

COVID-19 VACCINE-INDUCED ACUTE EXUDATIVE POLYMORPHOUS VITELLIFORM MACULOPATHY: CASE REPORTS.

BACKGROUND: Acute exudative polymorphous vitelliform maculopathy is a presumed retinal pigment epithelium abnormality that has been reported in patients with neoplasms and under certain classes of drugs. The pathophysiology remains unclear, despite the typical clinical features. PURPOSE: To report two cases of acute exudative polymorphous vitelliform maculopathy occurring after vaccination with a COVID-19 vaccine. CASE REPORTS: Two adult patients presented with visual disturbance after inoculation with a COVID-19 vaccine. The patients were otherwise healthy and have no family history of retinal dystrophies. Both cases exhibited the following features on multimodal imaging: multifocal hyporeflective lesions involving the macula, elongated photoreceptors, accumulated vitelliform material exhibiting autofluorescence, and lack of fluorescein dye leakage. Evidence of retinal pigment epithelium dysfunction was confirmed by electrooculography. CONCLUSION: Two cases of acute exudative polymorphous vitelliform maculopathy occurring after COVID-19 vaccination were reported. A relationship between the vaccine and the retinal pigment epithelial abnormality development that led to acute exudative polymorphous vitelliform maculopathy was postulate, possibly through autoantibodies against the severe acute respiratory syndrome coronavirus 2 virus structural surface glycoprotein antigens that cross react with the normal retinal pigment epithelial cells.

CHOROIDAL NEVUS ASSOCIATED WITH VITELLIFORM DEPOSITION IN A PATIENT WITH AUTOSOMAL DOMINANT BEST DYSTROPHY.

BACKGROUND/PURPOSE: To describe the clinical, optical coherence tomography (OCT), fundus autofluorescence and ultrasound findings of a patient with a choroidal nevus actively exuding vitelliform material in the setting of autosomal dominant Best dystrophy (BD). METHODS: The patient's clinical course was followed over time with ophthalmic examinations and multimodal imaging. RESULTS: A 71-year-old male patient with BD was referred for evaluation of a choroidal nevus in the right eye. Dilated fundoscopic examination showed a small pigmented choroidal nevus in the temporal periphery. Over a 3-year period, the nevus developed progressive deposition of vitelliform material along its inferior border. Meanwhile, OCT and fundus photography showed only slight growth. Ultrasound showed no change in height; basal measurements were confounded by the increased vitelliform deposits. Genetic testing confirmed a heterozygous mutation in the BEST1 gene and electrophysiology was consistent with BD. CONCLUSIONS: Dysfunction of the retinal pigment epithelium associated with BD may cause novel presentations of other conditions such as choroidal nevi. The implication for malignant transformation of a choroidal nevus associated with vitelliform deposit accumulation in this context is unknown.

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.

Clinical Correlation between Acute Exudative Polymorphous Paraneoplastic Vitelliform Maculopathy and Metastatic Melanoma Disease Activity: A 48-month Longitudinal Case Report.

PURPOSE: Longitudinal evaluation of acute exudative polymorphous paraneoplastic vitelliform maculopathy (AEPPVM) following diagnosis and treatment of metastatic melanoma. METHODS: Case report of a 47-year-old male with unknown primary metastatic melanoma and AEPPVM monitored before and during melanoma treatment using clinical exam, retinal imaging, and electroretinograms (ERG). Genetic testing and autoantibody panels were performed. RESULTS: He presented within a month of metastatic melanoma diagnosis with numerous bilateral vitelliform lesions in the posterior pole, consistent with AEPPVM. Metastatic disease was treated with immunotherapy, radiosurgery, and radiation over 48 months. Maculopathy and metastatic disease improved and worsened in parallel. Genetic testing was negative for bestrophin-1. An autoantibody panel was positive for anti-recoverin and transducin-α. CONCLUSION: AEPPVM is an uncommon paraneoplastic retinopathy found in patients with metastatic malignancy. To our knowledge, this is the first report demonstrating a temporal association between metastatic disease activity and quantifiable changes in retinal imaging over a 4-year period.

ACUTE EXUDATIVE POLYMORPHOUS VITELLIFORM MACULOPATHY ASSOCIATED WITH PRIMARY EPSTEIN-BARR VIRUS INFECTION.

PURPOSE: To report a case of acute exudative polymorphous vitelliform maculopathy associated with primary Epstein-Barr virus infection. METHODS: Multimodal imaging including color fundus photography, spectral-domain optical coherence tomography, blue-light fundus autofluorescence, fluorescein angiography, and indocyanine green angiography. RESULTS: A 24-year-old otherwise healthy woman presented with an acute bilateral visual disturbance associated with cervical lymphadenopathy. Spectral-domain optical coherence tomography showed bilateral foveal serous retinal detachment (SRD) with thickening of the ellipsoid zone throughout the posterior pole corresponding to hyperautofluorescence on fundus autofluorescence, faint diffuse hyperfluorescence on fluorescein angiography without leakage, and mild late hyperfluorescence on indocyanine green angiography. Systemic workup revealed an acute Epstein-Barr virus infection. Within several weeks, multifocal SRDs developed in the macula and paramacula. The SRDs then became increasingly hyperautofluorescent with spectral-domain optical coherence tomography showing subretinal hyperreflective material. This vitelliform material then slowly resolved while the thickness of the surrounding ellipsoid zone normalized. The fluorescein angiography and indocyanine green angiography appeared normal at Month 8. Visual acuity was 20/20 in both eyes at all times. No treatment was initiated. CONCLUSION: Acute exudative polymorphous vitelliform maculopathy may be associated with an acute Epstein-Barr virus infection. Acutely, multimodal imaging revealed findings consistent with RPE dysfunction and reduced photopigment density. Subsequent accumulation of vitelliform material gradually resolved over an 8-month follow-up.

THE ROLE OF CHECKPOINT INHIBITORS IN PARANEOPLASTIC ACUTE EXUDATIVE POLYMORPHOUS VITELLIFORM MACULOPATHY: REPORT OF TWO CASES.

PURPOSE: To report on two cases with paraneoplastic acute exudative polymorphous vitelliform maculopathy within one month after the initiation of nivolumab. METHODS: Case report. RESULTS: Two patients with metastatic mucosal melanoma were diagnosed with acute exudative polymorphous vitelliform maculopathy within one month after the initiation of the checkpoint inhibitor nivolumab. Both cases showed a neurosensory retinal detachment and subretinal hyperautofluorescent material, which persisted after discontinuation of nivolumab and treatment with local and/or systemic corticosteroids. In one case, nivolumab was introduced again in a later stage in combination with surgical reduction of the tumor, eventually leading to resolution of the subretinal lipofuscin-rich fluid. CONCLUSION: The development of paraneoplastic acute exudative polymorphous vitelliform maculopathy in melanoma patients can be triggered by treatment with nivolumab. However, achieving tumor control, which may involve continuation of nivolumab, could be the key to success.

Coronavirus Disease 2019-induced Acute Exudative Polymorphous Vitelliform Maculopathy.

Acute exudative polymorphous vitelliform maculopathy (AEPVM) is a rare entity characterized by acute multifocal macular detachment with polymorphous subretinal vitelliform deposits. The disease is a presumed retinal pigment epithelial dysfunction and is reported to occur with malignancies. We report a case of a 32-year-old otherwise healthy woman who presented with an acute bilateral visual disturbance a few days after testing positive for coronavirus disease 2019 (COVID-19). Her initial visual acuity was 6/6 in both eyes. Fundus examination revealed bilateral multifocal round yellowish subretinal deposits. Spectral-domain optical coherence tomography showed bilateral foveal serous retinal detachment with subretinal hyperreflective materials consistent with vitelliform deposits. Systemic workup to exclude malignancies and genetic diseases was unremarkable. The patient was observed without treatment, and the vitelliform materials gradually resolved over 18 months of follow-up. In our era of the global pandemic, AEPVM may be associated with COVID-19 infection.

Acute exudative polymorphous vitelliform maculopathy during pembrolizumab treatment for metastatic melanoma: a case report.

BACKGROUND: The use of immunomodulating therapy to treat various cancers has been on the rise and these immune checkpoint inhibitors are known to cause ocular side effects. In this article a case of acute exudative polymorphous vitelliform maculopathy (AEPVM) is reported which developed during a first line treatment with pembrolizumab. CASE PRESENTATION: A 54-year-old woman was referred because of blurry vision in both eyes with a yellow spot in the central visual field of the left eye. These symptoms started after four treatments with pembrolizumab (a monoclonal antibody against the programmed cell death receptor-1) for a metastatic recurrent vaginal mucosal melanoma. Her best corrected visual acuity was 10/10 in both eyes with a correction of + 2.00 bilaterally. There were no inflammatory findings in the anterior segment or the vitreous. Fundoscopy revealed an attenuation of the foveal reflex with subtle yellow-white subretinal macular deposits (vitelliform lesions) in both eyes. Fluorescein angiography did not show staining or leakage in the mid-phase, neither a late staining. Spectral-domain optical coherence tomography of the macula illustrated bilateral neurosensory retinal detachment with a thick, highly reflective band at the outer photoreceptor segment. En face structural OCT at the level of the photoreceptors showed focal areas of increased signal corresponding to hyperreflective vitelliform material. The treatment with pembrolizumab was ceased immediately. During the following visits we slowly saw an improvement of the neurosensory retinal detachment. After almost four months a total resolution of the subretinal fluid was visualized in both eyes without the use of additional treatment, though the vitelliform deposits persisted. CONCLUSIONS: The development of AEPVM in melanoma patients could be triggered by treatment with Pembrolizumab. Pembrolizumab has the potential to disturb indirectly the retinal pigment epithelium homeostasis with accumulation of lipofuscin deposits and subretinal fluid, both signs of AEPVM.

Association of Clinical and Genetic Heterogeneity With BEST1 Sequence Variations.

Importance: Detailed phenotypic information on the spectrum of fundus abnormalities and clinical variability of all phenotypes associated with sequence variations in BEST1 is limited. Objective: To report a detailed phenotypic and genetic analysis of a patient cohort with sequence variations in BEST1. Design, Setting, and Participants: This retrospective case series took place at the Oxford Eye Hospital in Oxford, UK. Thirty-six patients from a single center with disease-causing sequence variations in BEST1 from 25 different families were analyzed. Data were collected from November 2017 to June 2018, and analysis began April 2018. Main Outcomes and Measures: Results of ocular phenotyping and genetic testing using targeted next-generation sequencing to identify BEST1 sequence variations. Results: Thirty-six patients from 25 families with disease-causing sequence variations in BEST1 were included. Of 36 patients, 20 (55.6%) were female. Three distinct clinical phenotypes were identified: autosomal recessive bestrophinopathy (ARB), best vitelliform macular dystrophy (BVMD), and adult-onset vitelliform macular dystrophy. The ARB phenotype group comprised 18 patients from 9 families with age in years at symptom onset ranging from less than 10 to 40s. All patients showed a common phenotype of fundus autofluorescence abnormalities, and spectral-domain optical coherence tomography features were similar in all patients with schitic and cystoid changes. A phenotype of a beaten metallic retinal appearance extending from the mid periphery to the far periphery was identified in 8 patients. Four patients from 1 family with ARB were previously reported to have autosomal recessive retinitis pigmentosa but were reclassified as having ARB as part of this study. The BVMD phenotype group comprised 16 patients from 14 families with age at symptom onset ranging from less than 10 to 70s. Fundus features were localized to the macula and consistent with the stage of BVMD. In the adult-onset vitelliform macular dystrophy phenotype group, the age in years at symptom onset varied from 50s to 70s in 2 patients from 2 families. Fundus features included small vitelliform lesions. Where available, electro-oculogram results demonstrated a reduced or absent light rise in all patients with ARB and BVMD. Genetic testing identified 22 variants in BEST1. Conclusions and Relevance: These findings support the notion that ARB, BVMD, and adult-onset vitelliform macular dystrophy are clinically distinct and recognizable phenotypes and suggest that the association of autosomal recessive retinitis pigmentosa with sequence variations in BEST1 should be rereviewed.

Eight-year multimodal follow-up of recurrent idiopathic acute exudative polymorphous vitelliform maculopathy.

PURPOSE: To describe and analyze clinical findings in a patient with recurrent idiopathic acute exudative polymorphous vitelliform maculopathy (AEPVM), followed in detail, and to propose the diagnostic and follow-up algorithm. DESIGN: Retrospective observational analysis. PATIENT: A young adult male patient diagnosed with idiopathic AEPVM who developed two relapses in a 12-month period eight years after the initial onset. METHODS: Review of clinical charts, multimodal imaging, and electrophysiology findings. The patient repeatedly underwent complete ophthalmic examinations, including best-corrected visual acuity testing (BCVA), slit-lamp and fundus examinations; digital fundus photography, time-domain optical coherence tomography (OCT) in 2009 (Stratus OCT, Carl Zeiss Meditec, USA) and spectral-domain OCT in 2017-2018 (Spectralis-OCT, Heidelberg Engineering, Germany), together with fundus autofluorescence (FAF), fluorescein angiography (FA), and indocyanine green angiography (ICGA), all with HRA2 (Heidelberg Engineering, Germany); microperimetry (MP-1 microperimeter, Nidek, Japan). Laser flare photometry (Kowa FM-600, Japan) and electrophysiology testing were also performed. MAIN OUTCOME MEASURES: Clinical features of long-lasting recurrent idiopathic AEPVM, and diagnostic and follow-up algorithm in such rare cases. RESULTS: Case report of a 25-year-old male Caucasian patient with typical features of AEPVM, including serous neuroepithelial detachment with irregular retinal elevations, ophthalmoscopically resembling retinal folds, with subsequent subretinal accumulation of characteristic yellow-white vitelliform deposits. Features in this case rarely described, or even not yet reported, include indocyanine- and fluorescein-negative intraretinal cystic changes, optic disc hyperfluorescence on FA, serous retinal elevations mimicking retinal folds, increased choroidal thickness, lack of rapid visual recovery, and very slow anatomical improvement of the relapses. Bimonthly fundus autofluorescence evaluation together with SD-OCT were the most informative diagnostic methods, demonstrating the evolution of pathological signs. CONCLUSION: AEPVM may be a recurrent or even chronic condition with uncertain long-term visual outcomes. It may have variable clinical presentations depending on the stage of the disease, and both clinical manifestations and imaging features of different stages of the pathologic process may overlap. Patients should be made aware that visual improvement occurs very slowly, if at all. Bimonthly fundus autofluorescence evaluation together with SD-OCT should be recommended in such cases.

Recurrence of SRF Post Intravitreal Ranibizumab for Pediatric Choroidal Neovascularisation Secondary to Best Disease.

We present five cases of choroidal neovascularization secondary to pediatric Best disease which were treated with two different doses of intravitreal ranibizumab. Optical coherence tomography was used for monitoring of the cases. Three cases had subretinal fibrosis at presentation and two out of these 3 cases required repeat intravitreal ranibizumab at one year follow-up due to recurrence of subfoveal subretinal fluid.

A proposed mechanism influencing structural patterns in X-linked retinoschisis and stellate nonhereditary idiopathic foveomacular retinoschisis.

OBJECTIVE: To explore the structural differences between X-linked retinoschisis (XLR) and stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR) using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: A case series of two patients, a 9-year-old male with XLR and a 58-year-old woman with SNIFR were imaged with swept-source optical coherence tomography angiography (SS-OCTA; PLEX Elite 900, Carl Zeiss Meditec, Inc, Dublin, CA). Automated segmentation was manually adjusted to include the areas of retinoschisis within en face flow and structural slabs. The flow data were binarized using ImageJ 1.51s (Wayne Rasband, National Institutes of Health, USA, http://imagej.nih.gov.ij ) and superimposed onto the structural slab. RESULTS: In the eye with XLR, OCTA flow data superimposed on the structural slab demonstrated flow signal within numerous bridging structures connecting the inner and outer plexiform layers containing the intermediate (ICP) and deep (DCP) capillary plexuses. In contrast, the same technique applied to the eye with SNIFR demonstrated an absence of flow signal in the cystic retinal spaces within Henle's fiber layer. CONCLUSIONS: The vascular pattern of bridging vessels between the ICP and DCP is closely related to the structural "retinoschisis" pattern of XLR and appears to be structurally different from that seen in SNIFR. Moreover, the connecting vessels appear to be highly represented and regularly distributed, thereby supporting a serial arrangement of the retinal capillary plexuses within the perifoveal macula.

OCTA Imaging of Choroidal Neovascularization Treated Using Photodynamic Therapy in a Young Patient With Best Macular Dystrophy.

This study reports the onset of a choroidal neovascularization (CNV) in a young patient affected with Best macular dystrophy (BMD) using optical coherence tomography angiography (OCTA) and describes its changes after photodynamic therapy (PDT). In the patient's right eye (OD), OCTA scans demonstrated a large, tangled, and well-demarcated vascular network at the outer retinal (OR) and choriocapillaris (CC) layers. Best-corrected visual acuity (BCVA) was 20/40 OD. Twenty days after PDT, BCVA OD improved (20/30), and the macular hemorrhage was significantly reduced. OCTA showed regression of the vascular network both in the OR and CC layers, with a significant reduction of the internal anastomosis and connection in absence of ischemic complication at the choriocapillaris. The authors concluded that OCTA is the best imaging technique for precise diagnosis and follow-up of the choroidal neovascularization in children affected with BMD. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:969-973.].