Best Vitelliform Macular Dystrophy Natural History Study Report 1: Clinical Features and Genetic Findings.

PURPOSE: To analyze the genetic findings, clinical spectrum, and natural history of Best vitelliform macular dystrophy (BVMD) in a cohort of 222 children and adults. DESIGN: Single-center retrospective, consecutive, observational study. PARTICIPANTS: Patients with a clinical diagnosis of BVMD from pedigrees with a likely disease-causing monoallelic sequence variant in the BEST1 gene. METHODS: Data were extracted from electronic and physical case notes. Electrophysiologic assessment and molecular genetic testing were analyzed. MAIN OUTCOME MEASURES: Molecular genetic test findings and clinical findings including best-corrected visual acuity (BCVA), choroidal neovascularization (CNV) rates, and electrophysiologic parameters. RESULTS: Two hundred twenty-two patients from 141 families were identified harboring 69 BEST1 variants. Mean age at presentation was 26.8 years (range, 1.3-84.8 years) and most patients (61.5%) demonstrated deterioration of central vision. Major funduscopic findings included 128 eyes (30.6%) with yellow vitelliform lesions, 78 eyes (18.7%) with atrophic changes, 49 eyes (11.7%) with fibrotic changes, 48 eyes (11.5%) with mild pigmentary changes, and 43 eyes (10.3%) showing a vitelliruptive appearance. Mean BCVA was 0.37 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/47) for the right eye and 0.33 logMAR (Snellen equivalent, 20/43) for the left eye at presentation, with a mean annual loss rate of 0.013 logMAR and 0.009 logMAR, respectively, over a mean follow-up of 9.7 years. Thirty-seven patients (17.3%) received a diagnosis of CNV over a mean follow-up of 8.0 years. Eyes with CNV that received treatment with an anti-vascular endothelial growth factor (VEGF) agent showed better mean BCVA compared with eyes that were not treated with an anti-VEGF agent (0.28 logMAR [Snellen equivalent, 20/38] vs. 0.62 logMAR [Snellen equivalent, 20/83]). Most eyes exhibited a hyperopic refractive error (78.7%), and 13 patients (6.1%) received a diagnosis of amblyopia. Among the 3 most common variants, p.(Ala243Val) was associated with a later age of onset, better age-adjusted BCVA, and less advanced Gass stages compared with p.(Arg218Cys) and p.(Arg218His). CONCLUSIONS: BVMD shows a wide spectrum of phenotypic variability. The disease is very slowly progressive, and the observed phenotype-genotype correlations allow for more accurate prognostication and counselling. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Phenotypic and Genetic Spectrum of Autosomal Recessive Bestrophinopathy and Best Vitelliform Macular Dystrophy.

Purpose: Autosomal recessive bestrophinopathy (ARB) and vitelliform macular dystrophy (VMD) are distinct phenotypes, typically inherited through recessive and dominant patterns, respectively. Recessively inherited VMD (arVMD) has been reported, suggesting that dominant and recessive BEST1-related retinopathies represent a single disease spectrum. This study compares adVMD, arVMD, and ARB to determine whether a continuum exists and to define clinical and genetic features to aid diagnosis and management. Methods: One arVMD patient and nine ARB patients underwent standard ophthalmic examination, imaging, electrophysiology, and genetic assessments. A meta-analysis of reported BEST1 variants was compiled, and clinical parameters were analyzed with regard to inheritance and phenotype. Results: Among 10 patients with biallelic BEST1 variants, three novel ARB variants (p.Asp118Ala, p.Leu224Gln, p.Val273del) were discovered. A patient with homozygous p.Glu35Lys was clinically unique, presenting with VMD, including hyperautofluorescence extending beyond the macula, peripheral punctate lesions, and shortened axial-length. A tritan-axis color vision deficit was seen in three of six (50%) of ARB patients. Attempts to distinguish recessively-inherited ARB and dominantly-inherited VMD genotypically, by variant frequency and residue location, did not yield significant differences. Literature meta-analysis with principle component analysis of clinical features demonstrated a spectrum of disease with arVMD falling between adVMD and ARB. Conclusions: This study suggests that arVMD is part of a continuum of autosomal recessive and dominant BEST1-related retinopathies. Detailed clinical and molecular assessments of this cohort and the literature are corroborated by unsupervised analysis, highlighting the overlapping heterogeneity among BEST1-associated clinical diagnoses. Tritan-axis color vision deficit is a previously unreported finding associated with ARB.

SHORT-TERM MODIFICATIONS OF ELLIPSOID ZONE IN BEST VITELLIFORM MACULAR DYSTROPHY.

PURPOSE: To assess ellipsoid zone (EZ) alterations in Best vitelliform macular dystrophy using spectral-domain optical coherence tomography. METHODS: Prospective, observational case series. Forty-three patients (43 eyes) underwent complete ophthalmological examination at baseline and at 24 months: best-corrected visual acuity (BCVA), biomicroscopy, fundus photography, and spectral-domain optical coherence tomography were performed. Acquisition protocol included 19-line raster scan. Alterations in EZ were marked on spectral-domain optical coherence tomography, and the area was manually calculated on a near-infrared reflectance image. Three patterns were identified: A (decrease >0.25 mm2), B (±0.25 mm2), and C (increase >0.25 mm2). Primary outcome was to describe different patterns of EZ alteration. Secondary outcomes included their correlation with BCVA and the description of a central optically preserved islet. RESULTS: At baseline, altered EZ was identified in 40 eyes. Worse BCVA significantly correlated with larger EZ alterations but not with lesion extension on fundus photograph. Only "pattern-C" eyes unveiled BCVA worsening at follow-up. Optically preserved islet was detected in 16 eyes (37%), disclosing significantly better vision; its disappearance at follow-up (n = 7; 44% of 16 eyes) correlated with a decrease in BCVA. CONCLUSION: The assessment of EZ status might represent a valuable functional marker in Best vitelliform macular dystrophy because stable alterations and the maintenance of a central optically preserved islet are associated with better visual acuity.

Induced Pluripotent Stem Cell Modeling of Best Disease and Autosomal Recessive Bestrophinopathy.

PURPOSE: To understand the pathophysiology of Best disease (BD) and autosomal recessive bestrophinopathy (ARB) by establishing an in vitro model using human induced pluripotent stem cell (iPSC). MATERIALS AND METHODS: Human iPSC lines were generated from mononuclear cells in peripheral blood of one ARB patient, one autosomal dominant BD patient, and two normal controls. Immunocytochemistry and reverse transcriptase polymerase chain reaction in iPSC lines were conducted to demonstrate the pluripotent markers. After the differentiation of iPSC into functional retinal pigment epithelium (RPE), morphological characteristics of the RPE were evaluated using confocal microscopy and immunocytochemistry. The rates of fluid flow across iPSC-RPE monolayer were measured to compare apical to basal fluid transports by RPE. RNA sequencing was performed on iPSC-RPE to identify the differences in gene expression profiles, and specific gene sets were tested using Gene Set Enrichment Analysis. RESULTS: Morphological characteristics, gene expression, and epithelial integrity of ARB iPSC were comparable to those of BD patient or normal control. Fluid transport from apical to basal was significantly decreased in ARB iPSC-RPE compared with BD iPSC-RPE or control iPSC-RPE. Gene Set Enrichment Analysis confirmed that ARB iPSC-RPE exhibited significant enrichments of epithelial-mesenchymal transition gene set and TNF-α signaling via NF-κB gene set compared to control iPSC-RPE or BD iPSC-RPE. CONCLUSION: A human iPSC model of ARB showed a functional deficiency rather than anatomical defects. ARB may be caused by RPE dysfunction following BEST1 mutation.

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.

Inherited Macular Dystrophies in a Tertiary Care Centre.

BACKGROUND: Inherited macular dystrophies constitute a group of diseases characterized by bilateral central visual loss with symmetrical macular abnormalities usually presenting in the first two decades of life. The aim of this study were to find out the demographic characteristics and disease pattern of inherited retinal dystrophies in subjects attending retina outpatient department in a tertiary care center. METHODS: An observational study among twenty-six participants diagnosed as macular dystrophy visiting a tertiary care centre in Nepal, during January 2018 to June 2018 were included in the study. Detailed history, slit lamp examination, dilated fundus examination, coloured fundus photography, full field electroretinogram, multifocal electroretinogram, automated visual field and colour vision were done. RESULTS: A total of 52 eyes of 26 subjects were diagnosed with macular dystrophy. The male to female ratio was 1:1. The mean age of presentation was 28.38 years. Most common symptom was blurring of vision seen in 96.15%.The mean visual acuity was 0.67 log mar units in right eye and 0.71 log mar units in the left eye. The most common macular dystrophy was cone dystrophy followed by adult vitelliform macular dystrophy and Stargardts dystrophy. CONCLUSIONS: Cone dystrophy is the most common followed by Stargardt's disease and adult vitelliform macular dystrophy. Most presented in the first two decades of life and the most common presenting symptom was blurring of vision.

Altered ellipsoid zone reflectivity and deep capillary plexus rarefaction correlate with progression in Best disease.

AIMS: To evaluate the effects of neurovascular damage in patients with the typical vitelliform lesion of Best vitelliform macular dystrophy (BVMD) in the attempt to identify different progression patterns. METHODS: Prospective, observational case series. Patients in the vitelliform stage of BVMD and healthy controls underwent complete ophthalmological examination on a yearly basis, including best-corrected visual acuity (BCVA), biomicroscopy, optical coherence tomography (OCT) and OCT angiography (OCT-A). 4.5×4.5 mm OCT-A slabs were imported into ImageJ software and their vessel density (VD) was calculated. Similarly, the ellipsoid zone (EZ) was manually outlined and the reflectivity was measured above the vitelliform lesion and in the 500 µm external to it. Retinal pigment epithelium-Bruch's membrane complex was taken as internal reference. RESULTS: 34 eyes (24 patients) and 34 matched controls were included in the study. Mean follow-up was of 28.4±5.8 months, with 12 eyes showing signs of stage progression at the end follow-up. The EZ overlying the vitelliform lesion and in the peri-lesional area disclosed a significant reduction in reflectivity when compared with the foveal and para-foveal EZ of controls, respectively. VD resulted meaningfully decreased only at the deep capillary plexus. Of notice, more extensive EZ (reflectivity <0.7) and vascular alterations (VD <0.4) at baseline strongly correlated with worse BCVA and were associated with a more rapid progression at follow-up. CONCLUSIONS: Both EZ reflectivity and VD at deep capillary plexus may prove valuable biomarkers to assess BVMD severity and detect progression. In this view, 'rapid progressors' might benefit the most from timely genetic therapies in the future.

Neovascularized Best Disease in Child: Contribution of Optical Coherence Tomography Angiography.

Choroidal neovascularization (CNV) is a rare but severe complication in Best disease and autosomal recessive bestrophinopathy. However, the visualization of the neovascular membrane is difficult on fluorescein angiography (FA) and indocyanine green angiography (ICGA) because of dye leakage due to the accumulation of material. The authors' study reports a case series of pediatric Best disease where optical coherence tomography angiography (OCTA) contributed to the diagnosis of CNV and prompt treatment. Five eyes of three patients were included (two Best disease and one autosomal recessive bestrophinopathy). The mean age at diagnosis was 6.8 years ± 1.8 years (range: 5 years to 10 years). OCTA showed the typical "sea fan-shaped" neovascular membrane in all five eyes, whereas, in most cases, conventional imaging by FA and ICGA did not show clearly the neovascularization due to masking effect of the vitelliform material. OCTA seems to be a good alternative to diagnosing CNV in Best disease, especially in children, as it is a noninvasive, rapid technique for imaging, and does not require the administration of dyes. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:597-601.].

Generation of Best disease-derived induced pluripotent stem cell line (FRIMOi006-A) carrying a novel dominant mutation in BEST1 gene.

Best disease, also known as Best vitelliform macular dystrophy, is an autosomal dominant form of macular degeneration. Here, we have generated an induced pluripotent stem cell (iPSC) line derived from a Best disease patient carrying a new dominant mutation in the BEST1 gene. Skin fibroblasts were reprogrammed to iPSCs by the non-integrative Sendai-virus method. The iPSC line has been characterized preserving the BEST1 mutation, expressing the pluripotency markers and being capable to differentiate to endoderm, mesoderm and ectoderm in vitro.

Outer Retinal Alterations Associated With Visual Outcomes in Best Vitelliform Macular Dystrophy.

PURPOSE: To describe outer retinal structure in patients with Best vitelliform macular dystrophy (BVMD) using spectral-domain optical coherence tomography (OCT) and correlate these results with best-corrected visual acuity (BCVA) and patient age. DESIGN: Retrospective cross-sectional study. METHODS: Patients with molecularly confirmed BVMD were compared with normal control subjects (NCs). A complete clinical evaluation was performed, including BCVA, fundus photography, spectral-domain OCT, and fundus autofluorescence. Spectral-domain OCT images were analyzed to determine the stage of the lesion, the central macular thickness (CMT), the foveal outer nuclear layer (ONL) thickness, and tomographic structural changes. RESULTS: Forty-two patients with BVMD (42 eyes) with a molecular diagnosis and 42 NCs (42 eyes) were included. Clinical stages (Gass clinical classification) were distributed as follows: 4.8% for stage 1, 23.8% for stage 2, 16.6% for stage 3, 45.2% for stage 4, and 9.5% for stage 5. The presence of subretinal fluid and vitelliform material was noted in 76% and 79% of the BVMD eyes examined, respectively, and was not associated with BCVA modification (P = .758 and P = .968, respectively). The median ONL thickness was significantly lower compared with the NCs (P < .001). BCVA was significantly correlated with stage (R = 0.710; P < .01), age (R = 0.448; P < .01), CMT (R = -0.411; P < .01), and ONL thickness (R = -0.620; P < .01). The disruption of the external limiting membrane and the ellipsoid zone was associated with a decreased BCVA (P < .001 for both). Among the 32 eyes with subretinal detachment, photoreceptor outer segment length was significantly correlated with BCVA (R = -0.467; P < .01) and ONL thickness (R = 0.444; P = < .01). CONCLUSION: This study shows the correlation between BCVA, age, and spectral-domain OCT features in patients with BVMD. ONL thickness as well as photoreceptor outer segment length are relevant functional correlates and outcome measures to follow photoreceptor impairments and disease progression.

The electrooculogram.

The electrooculogram (EOG) measures the cornea-positive standing potential relative to the back of the eye. By attaching skin electrodes outside the eye near the lateral and medial canthus, the potential can be measured by having the patient move the eyes horizontally a set distance. The voltage becomes smaller in the dark, reaching its lowest potential after 8-12min, the so-called dark trough. When the lights are turned on, the potential rises, reaching a peak by about 10min. When the size of the light peak is compared to the dark trough, the normal ratio should be near 2:1. A light peak:dark trough ratio of less than 1.7 is considered abnormal. The origin of electrooculographic potentials is the pigment epithelium of the retina interacting with the midretina. The light rise of the potential requires both a normal pigment epithelium and normal midretinal function. The most common use of the electrooculogram is to confirm Best disease. Best disease is identified by the appearance of an egg-yellow fundus and can be confirmed by recording both an electroretinogram (ERG) and electrooculogram (EOG). The ERG will be normal and the EOG will be abnormal. The EOG is also used for tracking eye movement.

Novel BEST1 gene mutations associated with two different forms of macular dystrophy in Tunisian families.

BACKGROUND: Epidemiological studies of hereditary eye diseases allowed us to identify two Tunisian families suffering from macular dystrophies: Best vitelliform macular dystrophy (BVMD) and autosomal recessive bestrophinopathy (ARB). The purpose of the current study was to investigate the clinical characteristics and the underlying genetics of these two forms of macular dystrophy. METHODS: Complete ophthalmic examination was performed including optical coherence tomography, electroretinography, electrooculography and autofluoresence imaging in all patients. Genomic DNA was extracted from peripheral blood collected from patients and family members. RESULTS: Sanger sequencing of all exons of the BEST1 gene in both families identified two new mutations: a missense mutation c.C91A [p.L31 M] at the N-terminal transmembrane domain within the ARB family and a nonsense mutation C1550G (p.S517X) in the C-terminal domain segregating in the BVMD family. CONCLUSIONS: Several mutations of the BEST1 gene have been reported which are responsible for numerous ocular pathologies. To the best of our knowledge, it is the first time we report mutations in this gene in Tunisian families presenting different forms of macular dystrophy. Our report also expands the list of pathogenic BEST1 genotypes and the associated clinical diagnosis.

Novel Missense Mutations in BEST1 Are Associated with Bestrophinopathies in Lebanese Patients.

To identify Bestrophin 1 (BEST1) causative mutations in six Lebanese patients from three families, of whom four had a presumed clinical diagnosis of autosomal recessive bestrophinopathy (ARB) and two showed a phenotype with a single vitelliform lesion, patients were subjected to standard ophthalmic examinations. In addition, BEST1 exons and their flanking regions were amplified and sequenced by Sanger sequencing. Co-segregation and detailed bio-informatic analyses were performed. Clinical examination results were consistent with ARB diagnosis for all index patients showing multifocal vitelliform lesions and a markedly reduced light peak in the electrooculogram, including the two patients with a single vitelliform lesion. In all cases, most likely disease-causing BEST1 mutations co-segregated with the phenotype. The ARB cases showed homozygous missense variants (M1, c.209A>G, p.(Asp70Gly) in exon 3, M2, c.1403C>T; p.(Pro468Leu) in exon 10 and M3, c.830C>T, p.(Thr277Met) in exon 7), while the two patients with a single vitelliform lesion were compound heterozygous for M1 and M2. To our knowledge, this is the first study describing mutations in Lebanese patients with bestrophinopathy, where novel biallelic BEST1 mutations associated with two phenotypes were identified. Homozygous mutations were associated with multifocal lesions, subretinal fluid, and intraretinal cysts, whereas compound heterozygous ones were responsible for a single macular vitelliform lesion.

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.

Best Vitelliform Macular Dystrophy.

Best vitelliform macular dystrophy (VMD or BVMD) is one of the most common macular dystrophies, affecting 1 in 10,000 individuals. The clinical presentation varies, depending on the stage of the disease at which the patient presents, usually one of these five stages: Previtelliform Vitelliform (Figs. 16.1, 16.2, 16.3 and 16.4) Pseudohypopyon Vitelliruptive (Fig. 16.5) Atrophic.

Best Vitelliform Macular Dystrophy.

Autosomal recessive bestrophinopathy (ARB) results from a total absence of functional bestrophin-1 protein owing to two BEST1 mutations, one on each of the chromosomes. If present at an early age, the presenting feature could be decreased vision due to amblyopia. Refractive error is hyperopia, predisposing these eyes for acute angle-closure glaucoma. The yellowish lesions are larger and more extensive-extending beyond the arcades-than in the typical autosomal dominant Best disease. Some of the eyes also show numerous yellowish subretinal dots. Lesions are multifocal (Fig. 29.1). Subretinal fibrosis in the macular area is a common feature. Optical coherence tomography (OCT) may show cystoid changes in the neurosensory retina. Fundus autofluorescence (FAF): Increased AF reflects lipofuscin accumulation in the RPE; decreased AF reflects RPE atrophy. Electroretinography (ERG): As panretinal photoreceptor dysfunction progresses with advancing age, full-field (FF) ERG shows delayed rod and cone responses. Electrooculography (EOG): Abnormal Arden ratio.

Fibrotic pillar leads to focal choroidal excavation in Best vitelliform dystrophy.

PURPOSE: To study focal choroidal excavations in patients with Best vitelliform dystrophy using optical coherence tomography and their topographical relation with fibrotic pillars. METHODS: This is a retrospective cross-sectional study of consecutive patients diagnosed with Best vitelliform dystrophy at a tertiary eye care center. Records of patients with Best vitelliform dystrophy were reviewed for best-corrected visual acuity, color fundus photographs, shortwave autofluorescence, optical coherence tomography, and electrooculogram with special emphasis on the presence of focal choroidal excavation (FCE) and fibrotic pillar. Main outcome measure was to study the fibrotic pillar in relation to the FCE. RESULTS: Thirty-eight eyes of 19 patients with mean age of 34.6 years were enrolled in the study. FCE was seen in eight eyes of six patients. Two patients had bilateral FCE and all the FCEs were located in the area of vitelliform lesion. Six out of eight eyes with FCE were in vitelliruptive stage of disease; one was in pseudohypopyon stage and one in atrophic stage. A fibrotic pillar was seen lying directly above the FCE in seven eyes. In one eye, hyper-reflective material not amounting to fibrotic pillar was seen lying above the FCE. CONCLUSION: A focal choroidal excavation in the setting of Best vitelliform dystrophy is seen predominantly in the vitelliruptive stage of the disease. Fibrotic pillars appear to play a role in the formation of these FCEs.

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.