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.

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.

Retinal capillary hemangioblastoma and hemiretinal vein occlusion in a patient with primary congenital glaucoma: A case report.

The presence of retinal capillary hemangioblastoma and cerebellar hemangioblastoma in the context of Von Hippel-Lindau syndrome (VHL) is not characteristically associated with other ophthalmologic conditions. Here, we report the case of a 22-yearold female with a history of bilateral primary congenital glaucoma who presented with a right juxtapapillary retinal capillary hemangioblastoma and an old hemiretinal vein occlusion in which the retinal capillary hemangioblastoma was likely the contributing factor. Her systemic work up was positive for VHL syndrome and revealed the presence of a fatal large brainstem hemangioblastoma. To our knowledge, the association of VHL and congenital glaucoma and/or retinal venous occlusion has not been reported.

NEW OBSERVATIONS REGARDING THE RETINOPATHY OF GENETICALLY CONFIRMED KEARNS-SAYRE SYNDROME.

PURPOSE: To report novel retinal findings in Kearns-Sayre syndrome and correlate degree of retinopathy with other clinical findings. METHODS: Observational case series of patients from Saudi Arabia with retinal and neuroophthalmologic examinations, medical chart review, and mitochondrial genetic evaluation. RESULTS: The three unrelated patients had progressive external ophthalmoplegia and pigmentary retinopathy bilaterally. Muscle biopsy in two of the cases revealed mitochondrial myopathy. All three had abnormal findings on neuroimaging and modestly reduced visual acuity in both eyes with a variable pigmentary retinopathy. One of the patients had bilateral subretinal fibrosis with a full-thickness macular hole in the right eye. All three patients had single, large-scale mitochondrial DNA (mtDNA) deletions (5.0-7.6 kb in size) with blood mtDNA heteroplasmy levels ranging from below 20% to 57%. Severity of pigmentary retinopathy did not correlate with severity of progressive external ophthalmoplegia, but did correspond grossly with electroretinographic abnormalities, just as the degree of ocular motility restriction and ptosis in each patient correlated with the size of their extraocular muscles on neuroimaging. In addition, the size of the single, large-scale mtDNA deletion and level of mtDNA heteroplasmy corresponded with degree of ocular motility restriction but not with severity of retinopathy. CONCLUSION: Subretinal fibrosis and macular hole are novel retinal observations which expand clinical profile in Kearns-Sayre syndrome. Genetic testing for mtDNA deletions and heteroplasmy in blood, muscle biopsy, careful ocular and retinal examination including electroretinography, and imaging are indispensable tests for this condition.

ANTIANGIOGENICS IN CHOROIDAL NEOVASCULARIZATION ASSOCIATED WITH LASER IN CENTRAL SEROUS CHORIORETINOPATHY.

BACKGROUND/PURPOSE: To report characteristics and treatment outcome of choroidal neovascularization (CNV) secondary to laser photocoagulation and photodynamic therapy (PDT) in central serous chorioretinopathy. METHODS: Retrospective analysis of 12 eyes of 12 patients, who were diagnosed to have CNV secondary to laser photocoagulation or PDT for central serous chorioretinopathy. Collected data included demographic details, history of presenting illness, clinical examination details including visual acuity at presentation, and follow-up with imaging and treatment details. Main outcome measures were resolution of CNV activity at the last follow-up. Secondary outcomes included change in visual acuity at final follow-up from baseline, number of injections, treatment-free interval, and adverse events. RESULTS: This study included 12 eyes of CNV secondary to laser photocoagulation (8 eyes) and PDT (4 eyes). Mean age of study subjects was 47.6 ± 15.4 years (range 33-82) with 8 men and 4 women. Mean interval between laser photocoagulation/PDT and diagnosis of CNV was 23.9 ± 54.5 months. All subjects had unilateral CNV with classic CNV on fluorescein angiography. Eight eyes had extrafoveal CNV, and four eyes had juxtafoveal CNV. Baseline best-corrected visual acuity was 0.56 ± 0.51 (Snellen equivalent 20/60) logMAR, and final best-corrected visual acuity was 0.53 ± 0.51 (Snellen equivalent 20/60) logMAR with no significant difference (P = 0.84). All four eyes that presented with the CNV secondary to PDT group required additional PDT treatment because of poor response to antivascular endothelial growth factor therapy. At the last follow-up, only one patient in the laser group had active CNV; the remaining patients of both groups had scarred CNV. Mean follow-up duration was 22.4 ± 23.1 months. Mean number of injections was 3.16 ± 2.62. Longest treatment-free interval was 8.29 ± 11.4 months. CONCLUSION: Antivascular endothelial growth factor therapy appears to be safe and efficacious in CNVs secondary to laser photocoagulation and PDT. Choroidal neovascularizations secondary to PDT appear to be more resistant to antivascular endothelial growth factor therapy than those because of laser photocoagulation and required additional PDT.

Treatment of retinitis pigmentosa due to MERTK mutations by ocular subretinal injection of adeno-associated virus gene vector: results of a phase I trial.

MERTK is an essential component of the signaling network that controls phagocytosis in retinal pigment epithelium (RPE), the loss of which results in photoreceptor degeneration. Previous proof-of-concept studies have demonstrated the efficacy of gene therapy using human MERTK (hMERTK) packaged into adeno-associated virus (AAV2) in treating RCS rats and mice with MERTK deficiency. The purpose of this study was to assess the safety of gene transfer via subretinal administration of rAAV2-VMD2-hMERTK in subjects with MERTK-associated retinitis pigmentosa (RP). After a preclinical phase confirming the safety of the study vector in monkeys, six patients (aged 14 to 54, mean 33.3 years) with MERTK-related RP and baseline visual acuity (VA) ranging from 20/50 to <20/6400 were entered in a phase I open-label, dose-escalation trial. One eye of each patient (the worse-seeing eye in five subjects) received a submacular injection of the viral vector, first at a dose of 150 µl (5.96 × 10(10)vg; 2 patients) and then 450 µl (17.88 × 10(10)vg; 4 patients). Patients were followed daily for 10 days at 30, 60, 90, 180, 270, 365, 540, and 730 days post-injection. Collected data included (1) full ophthalmologic examination including best-corrected VA, intraocular pressure, color fundus photographs, macular spectral domain optical coherence tomography and full-field stimulus threshold test (FST) in both the study and fellow eyes; (2) systemic safety data including CBC, liver and kidney function tests, coagulation profiles, urine analysis, AAV antibody titers, peripheral blood PCR and ASR measurement; and (3) listing of ophthalmological or systemic adverse effects. All patients completed the 2-year follow-up. Subretinal injection of rAAV2-VMD2-hMERTK was associated with acceptable ocular and systemic safety profiles based on 2-year follow-up. None of the patients developed complications that could be attributed to the gene vector with certainty. Postoperatively, one patient developed filamentary keratitis, and two patients developed progressive cataract. Of these two patients, one also developed transient subfoveal fluid after the injection as well as monocular oscillopsia. Two patients developed a rise in AAV antibodies, but neither patient was positive for rAAV vector genomes via PCR. Three patients also displayed measurable improved visual acuity in the treated eye following surgery, although the improvement was lost by 2 years in two of these patients. Gene therapy for MERTK-related RP using careful subretinal injection of rAAV2-VMD2-hMERTK is not associated with major side effects and may result in clinical improvement in a subset of patients.

Posterior microphthalmos and papillomacular fold-associated cystic changes misdiagnosed as cystoid macular edema following cataract extraction.

PURPOSE: Novel spectral-domain optical coherence tomography (SD-OCT) findings in posterior microphthalmos (PM) include cystoid changes in the papillomacular fold (PMF). These changes may be misdiagnosed as cystoid macular edema (CME) and may trigger unnecessary treatment including intravitreal injections. We report a case that underscores this scenario aiming to increase awareness of this entity among ophthalmologists. METHOD: A case report. RESULTS: A 25-year-old male presented with a history of clear lens extraction in both eyes as a refractive procedure. Postoperatively, he was diagnosed with CME and received five intravitreal bevacizumab injections in each eye as well as oral diamox for persistent cystic spaces noted on OCT. He was referred to our institution with the diagnosis of non-responding CME. A complete ophthalmic evaluation, including ultrasonography and SD-OCT, confirmed the diagnosis of PM and PMF with cystic cavities in the PMF. A fluorescein angiogram disclosed absence of macular leakage or optic nerve head staining indicating that the cystic cavities seen on SD-OCT are not due to postoperative CME but are rather the intrinsic cystic changes commonly seen in eyes with PM and a PMF. These cystic cavities were incorrectly thought to represent postoperative CME, which triggered the unnecessary treatment and lack of response. CONCLUSION: Cystic-like cavities are a component of the PMF in PM eyes and may be misdiagnosed as CME, especially in a postoperative setting. This case underscores the importance of understanding the intrinsic features of the PMF in eyes with PM and may help increase awareness among ophthalmologists of such a potentially confusing scenario.

Intraocular pressure trends after intravitreal injections of anti-vascular endothelial growth factor agents for diabetic macular edema.

PURPOSE: To study intraocular pressure (IOP) trends and risk factors of IOP elevation after intravitreal anti-vascular endothelial growth factor injections in diabetic macular edema. METHODS: A retrospective review of 760 eyes treated with intravitreal anti-vascular endothelial growth factor injections for diabetic macular edema was performed. The rate and risk factors of IOP elevation were assessed. Intraocular pressure elevation was defined as an increase above baseline IOP by ≥ 6 mmHg, increase above baseline by > 20%, or IOP elevation to > 24 mmHg on 2 or more consecutive visits after treatment. When more than one pretreatment IOP reading was available, baseline IOP was calculated as the mean of the available pretreatment IOP readings (up to a maximum of three last IOP readings). Intraocular pressure elevation was considered transient unless it was maintained throughout the follow-up or required treatment (persistent elevation). RESULTS: Over a mean follow-up of 18 months, persistent and transient IOP elevation occurred in 44 (5.8%) and 53 (7%) eyes, respectively. The majority of eyes with persistent IOP elevation (70.4%) showed IOP elevation of > 20% from baseline. Only 13 eyes (1.71%) met the more strict criteria (> 6 mmHg from baseline or an IOP elevation > 24 mmHg). Final IOP was higher in the persistent IOP elevation group than the rest of the eyes (P < 0.001). Only the number of injections was associated with IOP elevation (P < 0.001). CONCLUSION: Persistent IOP elevation after intravitreal anti-vascular endothelial growth factor injections for diabetic macular edema is uncommon but may be associated with a higher number of injections.

High-power handheld blue laser-induced maculopathy: the results of the King Khaled Eye Specialist Hospital Collaborative Retina Study Group.

PURPOSE: To report various types of maculopathy caused by momentary exposure to a high-power handheld blue laser. DESIGN: Consecutive case series. PARTICIPANTS: Fourteen eyes of 14 patients. METHODS: Patients with a history of eye exposure to a blue laser device (450 nm and a power range of 150-1200 mW) to a single institution were included. Evaluation included a full ophthalmic examination, fundus photography, macular spectral-domain optical coherence tomography, and fundus fluorescein angiography. MAIN OUTCOME MEASURES: Analysis of the types of maculopathy and vitreoretinal pathologic features. RESULTS: All patients were young males. The most common setting for injury was accidental at play. The types of maculopathies encountered were: a full-thickness macular hole (FTMH) in 4 eyes, a premacular subhyaloid hemorrhage in 5 eyes, premacular sub-internal limiting membrane hemorrhage in 2 eyes, an outer retinal disruption at the fovea in 1 eye, an epimacular membrane in 1 eye, and a schisis-like cavity in 1 eye. Best-corrected Snellen visual acuity at presentation ranged from 20/40 to 4/200 (mean, 20/290). Only 4 eyes (29%) improved spontaneously with increase in vision, whereas 10 eyes (71%) required intervention. The latter consisted of neodymium:yttrium-aluminum-garnet hyaloidotomy in the 5 eyes with subhyaloid hemorrhage and pars plana vitrectomy (PPV) for the eyes with FTMH and epimacular membrane. All 4 FTMH were closed successfully after PPV. Final mean best-corrected visual acuity in all cases was 20/35 (range, 20/15-20/300). CONCLUSIONS: Exposure to high-power handheld laser devices can cause a variety of maculopathies that can reduce central vision permanently. Although vision may improve spontaneously, most cases require intervention. Unrestricted access to commercially available high-power handheld laser devices is dangerous and public awareness should be encouraged.

Iris neovascularization and neovascular glaucoma in neurofibromatosis type 1: report of 3 cases in children.

PURPOSE: To report the clinical findings and outcomes in 3 patients with neurofibromatosis 1 (NF1) and retinal vascular abnormalities that resulted in angle closure secondary to iris neovascularization and describe the histopathologic abnormalities in 1 case. PATIENTS AND METHODS: Retrospective case series of patients with NF1 and angle closure due to iris neovascularization secondary to retinal vascular abnormalities. Histopathologic analysis of an enucleated eye in 1 case. RESULTS: Three children whose age ranged from 5 to 10 years at presentation, developed unilateral retinal vascular abnormalities that resulted in iris neovascularization and angle closure with a wide range of intraocular pressures. Two patients had retinal vasoproliferative lesions of which the affected eye became blind in 1 patient and the other retained useful vision after treatment with intracameral Bevacizumab, ablation of the retinal lesions, and surgical treatment of the neovascular glaucoma. The third patient underwent enucleation and had pathologic evidence of retinal ischemia. CONCLUSIONS: A variety of retinal vascular lesions occurring in NF1 are capable of producing iris neovascularization, ectropion uvea, and neovascular glaucoma. Although a spectrum of serious complications resulting in total vision loss can occur, retention of useful vision is possible, in some cases, with aggressive treatment of the retinal lesions and associated neovascular glaucoma. This report highlights the need for careful examination of the posterior segment with special attention to peripheral retinal vascular abnormalities or tumors in young patients with NF1.

Macular hole in juvenile X-linked retinoschisis.

An 18 year-old male with no antecedent of trauma, systemic syndrome or myopia was referred for surgical treatment of a full thickness macular hole in the left eye. A more careful inspection revealed discrete foveal cystic changes in the fellow eye and subtle peripheral depigmented retinal pigment epithelial changes in both eyes. A spectral-domain optical coherence tomography (SD-OCT) scan confirmed, in addition to the full thickness macular hole in the left eye, microcystic spaces in the nuclear layers of both retinae. The diagnosis of X-linked retinoschisis was confirmed with a full field electroretinogram displaying the typical negative ERG. Macular holes are uncommon in the young and those complicating X-linked retinoschisis are rare. This report highlights the importance of investigating the presence of a macular hole in a young patient and illustrates the clinical and SD-OCT clues beyond the foveal center which led to the correct diagnosis of X-linked juvenile retinoschisis.

Characteristics of optic disc melanocytomas presenting with visual dysfunction.

OBJECTIVE AND DESIGN: A retrospective review study was designed to describe five cases of optic disc melanocytomas with tumor-related visual impairment. PARTICIPANTS: Five patients with optic disc melanocytoma presented with visual complaints to a tertiary eye hospital in Saudi Arabia. MATERIALS AND METHODS: Demographic and clinical data were analyzed, including the results of ocular examination, lesion laterality, best-corrected Snellen visual acuity, pupillary reflex, visual field testing, color fundus photography, fundus fluorescein angiography, and ophthalmic ultrasound. RESULTS: Visual dysfunction secondary to optic disc melanocytoma was identified. Case 1 had macular star edema with mild tumor enlargement, Case 2 had optic atrophy, Case 3 had juxtapapillary choroidal neovascular membrane with macular involvement, Case 4 had optic disc swelling with an enlarged blind spot, and Case 5 had a large altitudinal visual field defect. CONCLUSION: Although melanocytomas of the optic disc tend to have a benign behavior with slow evolution and stable vision, they may adversely affect visual function through a variety of mechanisms.

Bilateral optic disc swelling as the presenting sign of pheochromocytoma in a child.

Bilateral optic disc swelling in children is a relatively uncommon sign with a wide array of differential diagnoses. We describe a boy with bilateral optic disc swelling referred as a case of papilledema. However, upon careful ocular fundus examination, detection of discrete retinal nerve fiber layer and pigment epithelial changes at a distance from the optic discs raised the probability of malignant hypertension. This was confirmed by a simple blood pressure measurement. Judicious medical control of the hypertension and a full systemic evaluation led to successful surgical treatment of the inciting pheochromocytoma. A thorough history and meticulous clinical examination are irreplaceable, powerful diagnostic tools that can correctly direct the plan of management, thus preventing unnecessary investigations and delays or potentially serious complications.

Optical coherence tomography demonstration of Best's vitelliform macular dystrophy in a child.

Considering the importance of optical coherence tomography in clinical decision making, the veracity of these images is critical. The authors describe a 5-year-old girl with Best's vitelliform macular dystrophy of different stages of development in both eyes in which the optical coherence tomography appearance correlated well with both the staves of the disease and the visual function.

Early diagnosis of the papillorenal syndrome by optic disc morphology.

The morphology of optic disc dysplasia is the most consistent finding in the papillorenal syndrome, an autosomal-dominant syndrome of eye and kidney maldevelopment often associated with the PAX2 mutation. In the absence of a recognized family history, the diagnosis is typically not made until renal disease is evident. We report an infant whose characteristic fundus findings led to the early diagnosis of the papillorenal syndrome before the potential development of renal dysfunction.