Effect of silicone oil versus gas tamponade on macular layer microstructure after pars plana vitrectomy for macula on rhegmatogenous retinal detachment.

PURPOSE: To analyze structural changes in the macular retinal layers and sub-foveal choroidal thickness (SFCT) in eyes after macula-on rhegmatogenous retinal detachment (RRD) repair by pars plana vitrectomy with either silicone oil (SO) or gas tamponade, and the effect of these changes on visual acuity. PATIENTS AND METHODS: Retrospective study which included 26 eyes in the SO Group and 32 in the Gas Group. Optical coherence tomography (OCT) scans of the affected eyes were obtained before surgery, and 3 months after PPV in the Gas Group, and during silicone oil in situ and 3 months after SO removal, in the SO Group. Qualitative assessment of photoreceptor layer and foveal contour, along with quantitative assessment of macular retinal thickness and SFCT was performed. Postoperative OCT macular microstructural changes were recorded and correlated to corrected distance visual acuity (CDVA). Intraocular pressure (IOP) was measured preoperative and at 3 months post operative. RESULTS: There was a 2-line loss (from 20/28 preoperatively to 20/40 at final follow-up) of CDVA in the SO Group (p=0.051), while there was no statistically significant change in CDVA in the Gas Group (p=0.786). There was no significant correlation between CDVA loss and duration of silicon tamponade (r=-0.031, p=0.893). There was a statistically significant increase in IOP from its baseline to final follow-up of 0.7 mmHg in the SO Group (p=0.023) while there was no statistically significant change in IOP in the Gas Group. During silicone oil tamponade, there was approximately 11% and 5% of retinal and sub-foveal choroidal thinning respectively, which was moderately resolved following silicone oil removal. 20% (5/24) of eyes in the SO Group had qualitative flattening of foveal contour during SO tamponade that resolved after SO removal. CONCLUSION: Thinning of the macula was noticed after macula-on RRD repair with SO tamponade. Such thinning was only partially reversible after the removal of SO.

Clinical spectrum, genetic associations and management outcomes of Coats-like exudative retinal vasculopathy in autosomal recessive retinitis pigmentosa.

Background: Coats-like retinal vasculopathy in retinitis pigmentosa (RP) is rare. This study describes its clinical spectrum, management outcomes and genetic associations in patients with autosomal recessive RP (arRP).Materials and methods: Retrospective review of ophthalmic, multimodal imaging, genetic findings and treatment outcomes of arRP patients who developed Coats-like features. Identification of patients included searching a retinal dystrophy registry of 798 patients.Results: Ten eyes of six patients with arRP (4 males, 2 females, mean age 33 years) demonstrated Coats-like features, namely inferotemporal peripheral retinal telangiectasis combined with unilateral inferotemporal vasoproliferative tumor (VPT) in 4 eyes. Exudative retinal detachment (ERD) developed in five eyes of which four had VPT. Ablation of the vasculopathy using retinal laser photocoagulation and/or cryotherapy in eight eyes, allowed ERD and/or lipid exudation to decrease in seven eyes despite incomplete vasculopathy regression. Additional intravitreal triamcinolone acetonide injection in one eye failed to regress the ERD and associated VPT. Observation in one eye caused increased exudation. Six mutations, including three novel mutations, were found in CRB1, CNGB1, RPGR, and TULP1.Conclusions: Coats-like features in arRP range from retinal telangiectasis to VPTs with extensive ERD and occur predominantly in the inferotemporal retinal periphery. In addition to their classic association with CRB1 mutations, other genes are implicated. To the best of our knowledge, this is the first report describing CNGB1 mutations in Coats-like RP. Awareness of the vasculopathy spectrum is important, and timely ablation of the vasculopathy with long-term monitoring is recommended to prevent additional visual loss in RP patients.

Comparison of short-pulse subthreshold (532 nm) and infrared micropulse (810 nm) macular laser for diabetic macular edema.

The purpose of the study was to assess both anatomic and functional outcomes between short-pulse continuous wavelength and infrared micropulse lasers in the treatment of DME. This was a prospective interventional study from tertiary care eye hospital-King Khaled Eye Specialist Hospital (Riyadh, Saudi Arabia). Patients with center-involving diabetic macular edema were treated with subthreshold laser therapy. Patients in the micropulse group were treated with the 810-nm diode micropulse scanning laser TxCell (IRIDEX Corporation, Mountain View, CA, USA) (subthreshold micropulse-STMP group). Laser was applied according to recommendations for MicroPulse (125 microns spot size, 300 ms pulse duration and power adjustment following barely visible testing burn) in a confluent mode (low intensity/high density) to the entire area of the macular edema. Patients in the short-pulse group were treated with grid pattern laser with 20 ms pulse PASCAL laser 532 nm (TopCon Medical Laser Systems, Tokyo, Japan) with EndPoint algorithm, which was either 30% or 50% of testing burn (EndPoint 30% and EndPoint 50% groups, respectively). Main outcome measures included best-corrected visual acuity (BCVA in logMAR) and foveal thickness at baseline and the last follow-up visit at 6 months. There were 44 eyes in the micropulse group, 54 eyes in the EndPoint 50% group and 18 eyes in the EndPoint 30% group. BCVA for the whole cohort (logMAR) was 0.451 (Snellen equivalent 20/56) at baseline, 0.495 (Snellen equivalent 20/62) (p = 0.053) at 3 months, and 0.494 (Snellen equivalent 20/62) at the last follow-up (p = 0.052). Foveal thickness for the whole cohort was 378.2 ± 51.7 microns at baseline, 347.2 ± 61.3 microns (p = 0.002) at 3 months, and 346.0 ± 24.6 microns at the final follow-up (p = 0.027). As such the short-pulse system yields more temporary reduction in edema. Comparison of BCVA between baseline and 6 months for EndPoint 30%, EndPoint 50% and STMP groups was p = 0.88, p = 0.76 and p = 0.003, respectively. Comparison of foveal thickness between baseline and 6 months for EndPoint 30%, EndPoint 50% and STMP groups was p = 0.38, p = 0.22 and p = 0.14, respectively. We conclude that the infrared micropulse system seems to improve functional outcomes. When applied according to previously published reports, short-pulse system may yield more temporary reduction in edema while infrared micropulse system may yield slightly better functional outcomes.

Manifestation of Panuveitis after Intraocular Surgery in a Child with Blau Syndrome.

Blau syndrome (BS) is a rare granulomatous disease with autosomal dominant inheritance. It is characterized by a triad of dermatitis, arthritis, and recurrent uveitis. This case presents the onset of panuveitis in BS after intraocular surgery. A 10-year-old boy presented to the outpatient clinic with retinal detachment in the left eye after 6 years following early-onset cataract surgery. Bilateral panuveitis occurred 3 weeks after surgical repair and resulted in a total visual loss in the left eye and was persistent to conventional treatment in the right eye. Genetic testing revealed a mutation in NOD2 gene. The addition of adalimumab to the treatment regimen resulted in long-term uveitis control and maintenance of 20/70 vision in the right eye. We propose that NOD2-mediated inflammatory cascade can be activated by intraocular surgery and results in the manifestation of BS.

Incidence and Natural History of Retinochoroidal Neovascularization in Enhanced S-Cone Syndrome.

OBJECTIVE: We examined the incidence and natural history of macular retinochoroidal neovascularization (RCN) in enhanced S-cone syndrome (ESCS). DESIGN: Retrospective case series. METHODS: This single-center study included 14 of 93 patients with ESCS who had signs of active or inactive RCN in ≥1 eye. We conducted multimodal retinal imaging, full-field electroretinography, and molecular genetic analysis of NR2E3 gene. Our main outcome measures included the cumulative incidence of RCN in ESCS, type of RCN, and mode of evolution of RCN. RESULTS: Fourteen (15.1%) of 93 patients with ESCS had RCN in ≥1 eye at 2 to 27 years of age. All 22 RCNs (21 eyes of 14 patients) were macular. Twelve of the RCNs were active with exudates/hemorrhages. Of these, 5 appeared de novo in a subretinal location, with photographic evidence of no pre-existing lesions. The latter were compatible with type 3 neovascularization or retinal angiomatous proliferation and subsequently evolved into unifocal fibrotic nodules. The remaining active lesions all had some degree of pre-existing fibrosis and remained stable. Ten inactive fibrotic nodules, identical to end-stage de novo lesions, were found and were presumed to represent healed RCNs. CONCLUSIONS: RCN, a treatable condition, may occur as early as 2 years of age and may be much more common in patients with ESCS than previously estimated. It may be the primary cause of the unifocal submacular fibrosis that is commonly observed in this condition. Additional research is needed to establish the pathogenesis of RCN in patients with ESCS and its optimal management.

Minimally interface vitrectomy for rhegmatogenous retinal detachment with a single break in young patients.

PURPOSE: This study evaluates a new surgical technique consisting of minimal vitreous removal under air (minimal interface vitrectomy; MIV) to reduce postoperative complications while preserving the ability to address surgical factors at the retinal break. METHODS: This retrospective analysis examined the outcomes of minimal interface vitrectomies in consecutive cases, with a minimum 12-month follow-up period, of primary rhegmatogenous retinal detachment (RRD), recurrent RRD after pars plana vitrectomy (PPV), or failed surgery after primary scleral buckling surgery (SBS). RESULTS: Twelve eyes of 12 patients with RRD underwent MIV. The total surgical duration was 190-300 s (mean, 245.25 s). Eight (66.7%) eyes were treated with cryotherapy, and 4 (33.3%) with endolaser to seal the retinal break. Successful, complete retinal reattachment was achieved in all eyes and maintained during follow-up. No intra- or postoperative complications occurred and no patients developed inflammation or cataract during follow-up. CONCLUSION AND IMPORTANCE: We effectively removed traction and subretinal fluid and treated breaks with endolaser or cryotherapy by using a novel minimal interface vitrectomy technique in this selected population.

Long-term resolution of chronic macular edema after a single dose of intravitreal dexamethasone in familial retinal arterial macroaneurysm.

PURPOSE: To report a favorable effect of intravitreal dexamethasone implantation in Familial Retinal Arterial Macroaneurysms (FRAM). METHODS: Retrospective Case Report. RESULTS: A 32-year-old male who presented with bilateral retinal macroaneurysms. Whole Exome Sequencing (WES) revealed a homozygous c.830-1 G > A mutation in Insulin Growth Factor Binding Protein 7 (IGFBP7) gene, confirming the diagnosis FRAM. The left eye was lost in the course of the disease, whereas the right eye developed a persistent macular edema due to multiple leaking retinal arterial macroaneurysms and responded poorly to intravitreal ranibizumab and only partially to intravitreal aflibercept. Intravitreal dexamethasone implantation in the right eye, on the other hand, resulted in marked visual and structural improvement. CONCLUSION: Intravitreal dexamethasone injections have beneficial anatomical and visual outcomes in FRAM patients with persistent macular edema poorly responsive to intravitreal injections.

Incidence of Intraocular Lens Exchange after Cataract Surgery.

Intraocular lens (IOL) exchange after cataract surgery is unusual but may be associated with suboptimal visual outcome. The incidence of IOL exchange has not been consistently estimated. Such information is invaluable when counseling patients prior to cataract surgery. We examined the incidence of, and indications and risk factors for, IOL exchange after cataract surgery. We also assessed visual outcome of eyes that had an IOL exchange. A cohort design was used to estimate the incidence of IOL exchange and a case-control design to identify factors associated with it. All phacoemulsification surgeries with IOL (n = 17415 eyes) during 2010-2017 and those that had a subsequent IOL removal or replacement during the same time period were identified (n = 34 eyes). The incidence of IOL exchange was 2 per 1000 surgeries (95% confidence interval [CI] 1 to 3) over 8 years. Eyes that underwent subsequent IOL removal or replacement were compared with eyes that had cataract surgery only (n = 47) across demographic and clinical characteristics. In a binary logistic regression analysis, two factors were significantly associated with IOL exchange/removal: an adverse event during cataract surgery (adjusted odds ratio [aOR] 19.45; 95% CI 4.89-77.30, P < 0.001) and a pre-existing ocular comorbidity (aOR 10.70; 95% CI 1.69-67.63, P = 0.021). The effect of gender was marginally significant (P = 0.077). Eyes that underwent IOL exchange or explantation were nearly two and a half times more likely to have a final best-corrected visual acuity of <20/60 compared to those that had cataract surgery alone (adjusted RR 2.60 95% CI, 1.13-6.02; P = 0.025).

Sickle cell retinopathy. A focused review.

PURPOSE: To provide a focused review of sickle cell retinopathy in the light of recent advances in the pathogenesis, multimodal retinal imaging, management of the condition, and migration trends, which may lead to increased prevalence of the condition in the Western world. METHODS: Non-systematic focused literature review. RESULTS: Sickle retinopathy results from aggregation of abnormal hemoglobin in the red blood cells in the retinal microcirculation, leading to reduced deformability of the red blood cells, stagnant blood flow in the retinal precapillary arterioles, thrombosis, and ischemia. This may be precipitated by hypoxia, acidosis, and hyperosmolarity. Sickle retinopathy may result in sight threatening complications, such as paracentral middle maculopathy or sequelae of proliferative retinopathy, such as vitreous hemorrhage and retinal detachment. New imaging modalities, such as wide-field imaging and optical coherence tomography angiography, have revealed the microstructural features of sickle retinopathy, enabling earlier diagnosis. The vascular growth factor ANGPTL-4 has recently been identified as a potential mediator of progression to proliferative retinopathy and may represent a possible therapeutic target. Laser therapy should be considered for proliferative retinopathy in order to prevent visual loss; however, the evidence is not very strong. With recent development of wide-field imaging, targeted laser to ischemic retina may prove to be beneficial. Exact control of intraoperative intraocular pressure, including valved trocar vitrectomy systems, may improve the outcomes of vitreoretinal surgery for complications, such as vitreous hemorrhage and retinal detachment. Stem cell transplantation and gene therapy are potentially curative treatments, which may prevent retinopathy. CONCLUSIONS: There is lack of evidence regarding the optimal management of sickle retinopathy. Further study is needed to determine if recent progress in the understanding of the pathophysiology and diagnosis of sickle retinopathy may translate into improved management and outcome.

Accommodative esotropia and Brown syndrome in a girl with recessive geleophysic dysplasia.

Geleophysic dysplasia and Weill-Marchesani syndrome are acromelic dysplasias characterized by short stature, brachydactyly, and joint contractures. Recessive Weill-Marchesani syndrome typically includes spherophakia, but the ocular phenotype of recessive geleophysic dysplasia is not well defined. We describe the ocular phenotype of a girl with genetically confirmed recessive geleophysic dysplasia (biallelic ADAMTSL2 mutations). Features included high corneal astigmatism, accommodative esotropia, unilateral Brown syndrome, and no evidence for zonular disease at 12 years of age.

Severe retinal degeneration at an early age in Usher syndrome type 1B associated with homozygous splice site mutations in MYO7A gene.

PURPOSE: Usher syndrome is the most common cause of deafness associated with visual loss of a genetic origin. The purpose of this paper is to report very severe phenotypic features of type 1B Usher syndrome in a Saudi family affected by positive homozygous splice site mutation in MYO7A gene. METHODS: Affected siblings went through detailed history. Complete ophthalmic examination was done. Imaging with colour fundus photography, fundus autofluorescence (AF), and optical coherence tomography (OCT) scans was performed. Full field electroretinogram (ffERG) was recorded. Molecular genetic testing was done using next-generation sequencing. RESULTS: Visual acuity was more reduced (range 20/300-20/40) in older siblings (age>30 years), than in younger (age <30 years) siblings (range 20/70-20/25). OCT scans showed macular atrophy in all but one case that has cystoid macular edema (CME). AF demonstrated atrophy outside a small foveal area showing high signal. FfERG was flat in all cases. The homozygous splice site mutation c.470+1G>A in intron 5 of the MYO7A gene was detected in all affected siblings. CONCLUSIONS: This mutation manifested with advanced retinal degeneration at a young age. This may have implications regarding future gene therapy in Usher syndrome cases with this genotype.

Serous retinal detachment after panretinal photocoagulation for proliferative diabetic retinopathy: a case report.

BACKGROUND: Proliferative diabetic retinopathy is a major cause of visual impairment in working-age adults worldwide. Panretinal photocoagulation is a cornerstone in its management; however, it may include a range of side effects and complications, one of these being serous retinal detachment. To the best of our knowledge, this is the first report of the use of intravitreal injection of bevacizumab for serous retinal detachment after panretinal photocoagulation. CASE PRESENTATION: A 24-year-old Saudi man with poorly controlled type 1 diabetes presented with bilateral progressive proliferative retinopathy in spite of several sessions of panretinal photocoagulation. After one additional such session, he developed bilateral serous retinal detachment and vision loss, which was managed with a single bilateral intravitreal bevacizumab injection. The serous retinal detachment subsided with partial recovery of vision. CONCLUSIONS: Serous retinal detachment after panretinal photocoagulation for proliferative diabetic retinopathy is a rare complication nowadays. In this case, it seems that excessive photocoagulation exceeded the energy-absorbing capacity of the retinal pigment epithelium, leading to a disruption of the blood-retinal barrier. A single injection of bilateral intravitreal bevacizumab was sufficient to control the serous retinal detachment. This effect may have been due to a reduction of vascular leakage resulting from the mechanism of action of this drug. No complications were noted from the injection. Caution should be exerted when attempting bilateral panretinal photocoagulation.

Teleophthalmology image-based navigated retinal laser therapy for diabetic macular edema: a concept of retinal telephotocoagulation.

BACKGROUND: To determine the feasibility and efficacy of a retinal telephotocoagulation treatment plan for diabetic macular edema. METHODS: Prospective, interventional cohort study at two clinical sites. Sixteen eyes of ten subjects with diabetic macular edema underwent navigated focal laser photocoagulation using a novel teleretinal treatment plan. Clinic 1 (King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia) collected retinal images and fundus fluorescein angiogram. Clinic 2 (Palmetto Retina Center, West Columbia, SC, USA) created image-based treatment plans based on which macular laser photocoagulation was performed back at clinic 1. The primary outcome of the study was feasibility of image transfer and performing navigated laser photocoagulation for subjects with diabetic macular edema between two distant clinics. Secondary measures were change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) by spectral-domain optical coherence tomography at 3 months after treatment. RESULTS: The teleretinal treatment plan was able to be successfully completed in all 16 eyes. The mean logMAR BCVA at baseline was 0.49 ± 0.1, which remained stable (0.45 ± 0.1) 3 months after treatment (p = 0.060). The CRT improved from 290.1 ± 37.6 µm at baseline to 270.8 ± 27.7 µm 3 months after treatment (p = 0.005). All eyes demonstrated improvement in the area of retinal edema after laser photocoagulation, and no eyes demonstrated visual acuity loss 3 months after treatment. CONCLUSION: This study introduces the concept of retinal telephotocoagulation for diabetic macular edema, and demonstrates the feasibility and safety of using telemedicine to perform navigated retinal laser treatments regardless of geographical distance.

Three New PAX2 Gene Mutations in Patients with Papillorenal Syndrome.

Papillorenal syndrome (PAPRS; Mendelian Inheritance in Man [MIM] 120330) is an autosomal dominant disease characterised by the presence of congenital renal and optic nerve abnormalities associated with mutations of the PAX2 gene. In this article, the authors present four patients with PAPRS who are carriers of three new PAX2 mutations, as well as another patient with a possible non-pathogenic variant of the PAX2 gene. All patients were given a full neurophthalmological examination, and all patients underwent a genetic test for PAX2. Patients 1 and 2 presented with the classic signs of PAPRS: renal disease associated with a congenitally abnormal optic disc, whereas patients 3 and 4 only presented with a congenital optic nerve abnormality and no renal involvement. In patients 1 and 2, the optic nerves were affected by the presence of a central excavation within the optic disc, absence of the central retinal artery, as well as multiple cilioretinal arteries radiating from the periphery of the optic disc. Bilateral optic nerve pits were seen in patient 3, and lastly, in patient 4 there was the presence of superficial gliotic tissue on the left optic disc. All patients presented with a missense mutation in the PAX2 gene, where in patient 4 possibly being only a non-pathogenic variant of the gene. In conclusion, the authors present two patients with classic clinical signs of PAPRS, having two new PAX2 mutations, which until now have not been described in the current literature; another patient with a new PAX2 mutation showing only ocular manifestations of the disease, and lastly, a patient who is a carrier of a variant of the PAX2 gene has a congenitally abnormal optic disc, which is probably not related to PAPRS.

Association between Sickle Cell Trait and the Prevalence and Severity of Diabetic Retinopathy.

PURPOSE: To determine whether Sickle cell trait (SCT) is associated with an increased severity of diabetic retinopathy. METHODS: This was a single center retrospective study case control study of 100 eyes of 100 patients with diabetes mellitus (DM) with SCT (SCT group) and 100 eyes of 100 age-matched patients with DM without SCT (control group). The main outcome measure was the difference in the prevalence of sight threatening DR [here defined as diabetic macular edema (DME) and/or proliferative diabetic retinopathy (PDR)], between the SCT and control groups. Secondary outcome measures included differences in visual acuity, ocular comorbidities, intraocular pressure, glycemic control as assessed by random blood glucose measurement, diabetes duration, nephropathy, hyperlipidemia and hypertension. RESULTS: The SCT group had statistically significantly shorter duration of DM (median [25% quartile] 15 [8.3] years versus 20 [14.7] years, respectively)(P<0.001) and presented with statistically better metabolic control (mean difference 1.6 mmol/l, (95% confidence interval [CI], 0.1-3.3;P = 0.03). The prevalence of PDR and/or DME was significantly lower in the SCT group (58%) compared to the control group, (95%)(P<0.001). The absence of SCT (adjusted odds ratio [AOR] = 24; 95% CI, 8-72; P<0.001) and longer duration of DM (AOR = 1.1 [95% CI, 1.02-1.13]; P = 0.003) were independent predictors of PDR and/or DME. CONCLUSIONS: SCT seems to protect against the development and progression of DR. This may have implications for monitoring and screening. Prospective studies are required to confirm this association. If true, this association may indicate an increased blood glucose buffering capacity of abnormal hemoglobin.

Update on Clinical Trials in Dry Age-related Macular Degeneration.

This review article summarizes the most recent clinical trials for dry age-related macular degeneration (AMD), the most common cause of vision loss in the elderly in developed countries. A literature search through websites https://www.pubmed.org and https://www.clinicaltrials.gov/, both accessed no later than November 04, 2015, was performed. We identified three Phase III clinical trials that were completed over the recent 5 years Age-Related Eye Disease Study 2 (AREDS2), implantable miniature telescope and tandospirone, and several other trials targeting a variety of mechanisms including, oxidative stress, complement inhibition, visual cycle inhibition, retinal and choroidal blood flow, stem cells, gene therapy, and visual rehabilitation. To date, none of the biologically oriented therapies have resulted in improved vision. Vision improvement was reported with an implantable mini telescope. Stem cells therapy holds a potential for vision improvement. The AREDS2 formulas did not add any further reduced risk of progression to advanced AMD, compared to the original AREDS formula. Several recently discovered pathogenetic mechanisms in dry AMD have enabled development of new treatment strategies, and several of these have been tested in recent clinical trials and are currently being tested in ongoing trials. The rapid development and understanding of pathogenesis holds promise for the future.

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.

Ocular phenotype analysis of a family with biallelic mutations in the BEST1 gene.

PURPOSE: To investigate the genetic cause and perform a comprehensive clinical analysis of a Danish family with autosomal recessive bestrophinopathy; to investigate whether Bestrophin may be expressed in normal human retina. DESIGN: Retrospective clinical and molecular genetic analysis and immunohistochemical observational study. METHODS: setting: National referral center. participants: A family with 5 individuals and biallelic BEST1 mutations, and enucleated eyes from 2 individuals with nonaffected retinas. observation procedures: Molecular genetic analysis included sequencing of BEST1 and co-segregation analysis. Clinical investigations included electro-oculography, full-field electroretinography, multifocal electroretinography, spectral-domain optical coherence tomography, and fundus autofluorescence imaging. Immunohistochemical analysis was performed. main outcome measures: BEST1 mutations, imaging findings, electroretinography amplitudes, and implicit times. RESULTS: The index case was compound heterozygous for p.A195V and a novel 15 base pair deletion leading to p.Q238L. The index case at age 10 demonstrated multifocal vitelliform changes that were hyperautofluorescent, cystoid macular edema in the inner nuclear layer, no light rise in the electro-oculography, and a reduced central but preserved peripheral retinal function by multifocal electroretinography. Full-field electroretinography demonstrated a reduced rod response and inner retina dysfunction. Retinal structure was normal in all 3 family members who carried a sequence change in BEST1. Electro-oculography light peak was reduced in both the mother and sister (heterozygous for p.Q238L). Immunohistochemistry could not confirm the presence of Bestrophin in normal human retina. CONCLUSIONS: Because of a relatively well preserved retinal function, autosomal recessive bestrophinopathy may be a suitable first candidate, among the BEST1-related ocular conditions, for gene replacement therapy.

Frequency, genotype, and clinical spectrum of best vitelliform macular dystrophy: data from a national center in Denmark.

PURPOSE: To estimate the prevalence, genotype, and clinical spectrum of Best vitelliform macular dystrophy (Best disease). DESIGN: Retrospective epidemiologic and clinical and molecular genetic observational study. METHODS: setting: National referral center. participants: Forty-five individuals diagnosed with Best disease. observation procedures: Retrospective review of patients diagnosed according to clinical findings and sequencing of BEST1. Patients with recently established molecular genetic diagnosis were followed up including multifocal electroretinography (mfERG), spectral-domain optical coherence tomography (SD-OCT), and fundus autofluorescence (FAF) imaging. main outcome measures:BEST1 mutations, SD-OCT and FAF findings, mfERG amplitudes, prevalence estimate of Best disease. RESULTS: BEST1 mutations described previously in Danish patients with Best disease are reviewed. In addition, we identified a further 8 families and 1 sporadic case, in whom 6 BEST1 missense mutations were found, 4 of which are novel. The mutation c.904G>T (p.Asp302Asn) was identified in members of 4 unrelated families. Structural alterations ranged from precipitate-like alterations at the level of the photoreceptor outer segments (OS) to choroidal neovascularization. The extent of the former correlated with the reduction of retinal function. A prevalence estimate of Best disease in Denmark based on the number of diagnosed cases was 1.5 per 100 000 individuals. CONCLUSIONS: Our data expand the mutation spectrum of BEST1 in patients with Best disease. Alterations of the OS overlying lesions with subretinal fluid are similar to those seen in central serous retinopathy and may indicate impaired turnover of OS. Our frequency estimate confirms that Best disease is one of the most common causes of early macular degeneration.