Peripheral retinal vasculopathy in childhood glaucoma.

PURPOSE: To report wide-field fluorescein angiography findings in the peripheral retina of eyes with childhood glaucoma. METHODS: Fluorescein angiograms were examined retrospectively in 12 patients with childhood glaucoma who underwent wide-field fluorescein angiography after surgical or medical treatment of glaucoma. This series included 12 eyes of 6 patients with primary congenital glaucoma, 5 eyes of 3 patients with glaucoma associated with congenital cataract surgery, 4 eyes of 2 patients with glaucoma associated with a systemic condition, and 1 eye of 1 patient with phakomatosis pigmentovascularis Type II. RetCam fundus photography images and digital fluorescein angiography were performed under general anesthesia. RESULTS: The most common finding observed in our series was peripheral retinal nonperfusion, which affected 20 eyes (91%). Other notable features seen were circumferential branching of the retinal vessels parallel to the ora serrata (77%), venous shunts (50%), and abnormal capillary branching patterns, including capillary dilatation (41%) and tortuous capillary tangles (18%). Leakage at the junction of vascular and avascular retina was not commonly seen (13.6%). None of the eyes had evidence of retinal neovascularization or fibrovascular proliferation. CONCLUSION: Retinal vascular abnormalities and peripheral nonperfusion are novel findings in childhood glaucoma. Further studies are needed to understand the significance and possible long-term consequences of these findings.

Retinoblastoma.

PURPOSE OF REVIEW: Retinoblastoma is the most common malignant intraocular tumor of childhood. Treatment and diagnostic modalities associated to this condition are changing rapidly as our understanding of this condition crystallizes. The purpose of this review is to provide an update of the current understanding of retinoblastoma. RECENT FINDINGS: Knowledge on tumorigenesis and genomic expression has expanded tremendously with the development of a mouse model for retinoblastoma. Tumor hypoxia has been identified as a significant step in the tumor progression and a novel target for future treatments. Current globe-sparing therapies, including periocular carboplatin, selective ophthalmic artery chemoreduction, intravitreal melphalan, and focal consolidation are being used and investigated actively. Diagnosis and the management of retinoblastoma is also undergoing major advances including wide-field photography, autofluorescence, and high-resolution optical coherence tomography. SUMMARY: Progressive advances in the understanding of retinoblastoma pathogenesis continue to lead treatment strategies. Improvements in the diagnosis and management of retinoblastoma are improving morbidity and mortality associated to this condition in the developed nations. However, it is of outmost importance to flatten the international boundaries to offer prompt care to retinoblastoma children in underdeveloped communities.

Laser treatment for retinopathy of prematurity.

Retinal development involves a complex coordination of events that may be affected by premature delivery, leading to retinopathy of prematurity (ROP), a potential blinding childhood disease. The avascular retina drives further disease progression, with laser ablation reducing unfavorable anatomic outcomes as well as maintaining visual acuity. Trials have stressed the importance of early identification and treatment of threshold and high-risk prethreshold disease to improve outcomes. Retinal ablation with laser photocoagulation should involve entire treatment of avascular retina with a confluent laser spot density, avoiding skip lesions. The current review highlights the use of laser photocoagulation in the treatment of ROP.

Lasers for the treatment of intraocular tumors.

Lasers are used extensively in ophthalmology for a variety of conditions, including many choroidal and retinal tumors. With technologic advances, current therapy attempts not only to maximize survival with globe-salvaging treatment, but also to preserve vision. Each neoplasm has different indications for primary and adjuvant therapy, as well as differing laser treatment protocols. Additionally, there are numerous laser applications available for use, including laser photocoagulation, transpupillary thermotherapy (TTT), and photodynamic therapy (PDT). The current review outlines the basic principles of laser treatment for intraocular tumors, focusing on the indications, treatment protocols, efficacy, and safety, while also presenting the latest advances in intraocular tumor treatment.

Intraoperative OCT of a full-thickness macular hole before and after internal limiting membrane peeling.

A child with a traumatic full-thickness macular hole was imaged perioperatively using spectral-domain optical coherence tomography (SD-OCT). Intraoperative imaging using a portable SD-OCT device equipped with a handheld probe demonstrated the full-thickness macular hole to be nearly completely closed following vitrectomy and internal limiting membrane peeling. Air was used as a tamponade agent and prone positioning was used postoperatively for 2 days. SD-OCT imaging confirmed closure of the full-thickness macular hole 5 days and 1 month postoperatively.

Evaluation of a computer-based system for plus disease diagnosis in retinopathy of prematurity.

OBJECTIVE: To measure accuracy and reliability of the computer-based Retinal Image Multiscale Analysis (RISA) system compared with those of recognized retinopathy of prematurity (ROP) experts, for plus disease diagnosis. DESIGN: Evaluation of diagnostic test or technology. PARTICIPANTS: Eleven recognized ROP experts and the RISA image analysis system interpreted a set of 20 wide-angle retinal photographs for presence of plus disease. METHODS: All experts used a secure Web site to review independently 20 images for presence of plus disease. Images were also analyzed by measuring individual computer-based system parameters (integrated curvature [IC], diameter, and tortuosity index) for arterioles and venules and by computing linear combinations and logical combinations of those parameters. Performance was compared with a reference standard, defined as the majority vote of experts. MAIN OUTCOME MEASURES: Diagnostic accuracy was measured by calculating sensitivity, specificity, and receiver operating characteristic area under the curve (AUC) for plus disease diagnosis by each expert, and by each computer-based system parameter, compared with the reference standard. Diagnostic agreement was measured by calculating the mean kappa value of each expert compared with all other experts and the mean kappa value of each computer-based system parameter compared with all experts. RESULTS: Among the 11 experts, sensitivity ranged from 0.167 to 1.000, specificity ranged from 0.714 to 1.000, AUC ranged from 0.798 to 1.000, and mean kappa compared with all other experts ranged from 0.288 to 0.689. Among individual computer system parameters, arteriolar IC had the highest diagnostic accuracy, with sensitivity of 1.000; specificity, 0.846; and AUC, 0.962. Arteriolar IC had the highest diagnostic agreement with experts, with a mean kappa value of 0.578. CONCLUSIONS: A computer-based image analysis system has the potential to perform comparably to recognized ROP experts for plus disease diagnosis.

Accuracy and reliability of remote retinopathy of prematurity diagnosis.

OBJECTIVE: To determine the accuracy and reliability of retinopathy of prematurity (ROP) diagnosis using remote review of digital images by 3 masked ophthalmologist readers. METHODS: An atlas was compiled of 410 retinal photographs from 163 eyes of 64 low-birth-weight infants taken using a wide-angle digital fundus camera. All the images were independently reviewed by 3 readers, and the diagnosis in each eye was classified into 1 of 4 ordinal categories: no ROP, mild ROP, type 2 prethreshold ROP, or ROP requiring treatment. Findings were compared with a reference standard of dilated indirect ophthalmoscopy with scleral depression performed by an experienced pediatric ophthalmologist. RESULTS: Sensitivities/specificities of the diagnosis of any ROP were 0.845/0.910 for the first reader, 0.816/0.955 for the second reader, and 0.864/0.493 for the third reader. Sensitivities/specificities of the diagnosis of ROP requiring treatment were 0.850/0.960 for the first reader, 0.850/0.973 for the second reader, and 0.900/0.953 for the third reader. When ROP was classified into ordinal categories, the overall weighted kappa for interreader reliability was 0.743. Intrareader reliability for detection of low-risk prethreshold ROP or worse was 100% for all readers. CONCLUSION: The accuracy, interreader reliability, and intrareader reliability of remote diagnosis of clinically relevant ROP based on digital imaging are substantial.

Retinopathy of Prematurity Versus Familial Exudative Vitreoretinopathy: Report on Clinical and Angiographic Findings.

BACKGROUND AND OBJECTIVE: Retinopathy of prematurity (ROP) and familial exudative vitreoretinopathy (FEVR) are classified as distinct diseases; however, emerging genetic research and fluoresce-in angiographic evidence suggest a margin of overlap between the two. PATIENTS AND METHODS This was an institutional review board-approved, retrospective case series. A literature review was performed, and medical records of all pediatric patients who underwent examination under anesthesia and laser for FEVR at the Bascom Palmer Eye Institute Pediatric Retina Service by one of the authors (AMB) from Jan. 1, 2006, to June 30, 2013, were analyzed retrospectively. RESULTS: Nine infants born prematurely had fluorescein angiograms and a clinical course most consistent with FEVR. Angiographic findings included irregular sprouts of vascularization at the vascular/ avascular junction, distinct pruning of vessels, pinpoint areas of hyperfluorescence, and segmental areas of vascular leakage. CONCLUSION: The authors propose a classification of ROPER (ROP vs. FEVR) to more accurately stratify these patients. Identification of this subset of patients will allow for sustained surveillance of infants with ROPER who demonstrate a continuing risk of disease activity.

Laser treatment of Coats' disease.

A 9-year-old boy presented with an exudative retinal detachment, vascular telangiectasias, subretinal lipid, and retinal macrocyst formation. He underwent three sessions of large-spot diode laser for the treatment of Coats' disease. Serial examinations and fundus photography documented an excellent involutional response with an improvement in visual acuity.

Hemorrhage as a sign of treatment failure after intra-arterial chemotherapy in retinoblastoma.

Intra-arterial melphalan chemotherapy (IAC) continues to demonstrate excellent utility in the treatment of retinoblastoma. We present the case of a 3-month-old boy diagnosed with with unilateral, advanced stage 5B retinoblastoma and a Coats' response in the right eye. After laser therapy he received 3 doses of IAC. Intraretinal hemorrhaging, first noted after the second dose and worsening after the third, preceded complex exudative retinal detachment. With little visual potential and evidence of atropy, the eye was enucleated. This case illustrates that intraretinal hemorrhage may serve as an early predictor of treatment failure.

Clinical and Electrophysiologic Characteristics of a Large Kindred with X-Linked Retinitis Pigmentosa Associated with the RPGR Locus.

PURPOSE: To phenotypically and genotypically characterize a large Puerto Rican kindred with X-linked retinitis pigmentosa associated with a novel RP GTPase regulator (RPGR) genotype. METHODS: A total of 100 family members of a single kindred with X-linked RP were evaluated with ophthalmic examinations and blood DNA analysis. Visual fields, OCT, and full-field ERG were obtained on all affected males and carriers. RESULTS: Of the 100 family members examined, 13 were affected males and 18 were carriers. A deletion of 2 base pair of the RPGR gene in the ORF15 region at position c.2267-2268 (Lys756del2aaAG hemi) was identified with the affected and carriers. Best eye visual acuity was correlated with age (Spearman coefficient = 0.95) with hand-motion acuity by age 35 and light perception to no light perception by age 50-60. Visual fields were minimally plottable by age 40, and ERG responses reached non-detectable levels by late teens. Carriers had no or mild visual symptoms. All carriers had visual acuity of at least 20/50 or better in one eye, and the amount of retinal degeneration was variable with ERG responses ranging from severely impaired to normal. CONCLUSIONS: Profound visual loss occurred by the second decade of life with progression to near no light perception by age 60 in this kindred of X-linked RP associated with the RPGR genotype. Female carriers maintained visual acuity with age and were identifiable by clinical and ERG examination. The information from this study is important to determine the optimal age for intervention, as new RP treatments are being developed and tested.

The Ocular Hypertension Treatment Study: reproducibility of cup/disk ratio measurements over time at an optic disc reading center.

PURPOSE: To determine the reproducibility over time of visual estimates of the horizontal cup/disk ratio by trained technicians from optic disk stereophotographs. METHODS: Baseline optic disk stereophotographs are graded at entry and regraded annually in a masked fashion. The 1,636 participants in the Ocular Hypertension Treatment Study (OHTS) undergo stereoscopic optic disk photography at study entry and annually thereafter. Stereophotographs are graded independently by two technicians at the Optic Disc Reading Center. If the readers' estimates of horizontal cup/disk ratio differ by more than 0.2 disk diameters (DD), they attempt to reach a consensus; if they cannot, the horizontal cup/disk ratio is adjudicated by a glaucoma specialist. RESULTS: The percent of regradings differing by 0.2 DD or more from the estimate of horizontal cup/disk ratio made at entry was 4%, 6%, and 7%, respectively at years 1, 2, and 3. The percent differing by more than 0.2 DD was 1% or less at all years. Intraclass correlation coefficients were 0.93, 0.92, and 0.92, respectively. Estimates of horizontal cup/disk ratio from sequential full-frame photographs and simultaneous split-frame photographs appeared comparable and equally reproducible. Gradings by technicians were comparable to gradings by glaucoma specialists. CONCLUSIONS: High reproducibility between repeated gradings of baseline horizontal cup/disk ratio was achieved by trained technicians adhering to a rigorous protocol. Horizontal cup/disk ratio measurements in OHTS are sufficiently reproducible to provide information about the relationship of cup/disk ratio to the prognosis of individuals with ocular hypertension.

Telephotoscreening to detect retinopathy of prematurity: preliminary study of the optimum time to employ digital fundus camera imaging to detect ROP.

PURPOSE: Labor-intensive screening of infants in the neonatal intensive care units is the only way presently to detect retinopathy of prematurity (ROP). Our purpose is to determine if RetCam 120 images (Massie Research Laboratories, Inc, Dublin, Calif), acquired by a neonatal nurse, can be used to screen for ROP by performing 2 screening sessions, at 32 to 34 weeks' (examination 1) and 38 to 40 weeks' (examination 2) postconceptional age. METHODS: RetCam examinations were performed by a nurse on infants at examination 1 and examination 2 intervals. At the same time, an examination was performed by an experienced ophthalmologist. Masked readers evaluated the digital images for the presence of ROP and, if ROP was present, estimated the risk of that eye progressing to prethreshold or threshold disease. The data were compared to the eye's clinical course. RESULTS: A total of 46 eyes were assessed at examination 1 and 50 eyes at examination 2 from July 1, 1999, to December 15, 1999. For detecting ROP, the sensitivity and specificity were 46% and 100% for examination 1 and 76% and 100% for examination 2. Sensitivity and specificity of predicting prethreshold was 64% and 97%, respectively, for examination 1 and 2. Sensitivity for predicting ROP threshold at examination 1 was 0% (only 1 photo was available for grading of sensitivity) and specificity for predicting ROP threshold at examination 1 was 95%. At examination 2, sensitivity and specificity were 100%. CONCLUSION: The RetCam examination had insufficient sensitivity to be recommended as a substitute for indirect ophthalmoscopy in screening for ROP. Reasons for low sensitivity are the technical limitation of the camera design itself, which creates difficulty in photographing the peripheral retina in small eyes, and the need for a lid speculum better adapted to the contact camera optical system design. Both of these issues are being addressed as part of an ongoing project to study the feasibility of employing telemetry of digital fundus images from remote, underserved neonatal intensive care units to ophthalmologists capable of diagnosing ROP.

Best's vitelliform macular dystrophy in 10- and 31-month-old siblings.

There are limited reports of Best's disease in children younger than 3 years. This is a case series of two family members aged 10 and 31 months with Best's disease. To the authors' knowledge, the 10-month-old male infant is the youngest patient with Best's disease documented by fundus photography.

Retinoschisis in the setting of Coats' disease.

This is a report of a 5-year-old boy who presented with an exudative retinopathy consistent with Coats' disease. Optical coherence tomography confirmed the concurrent presence of retinoschisis in the same eye, adjacent to the areas of exudation and ischemia. Treatment with laser photocoagulation, corticosteroids, and anti-VEGF therapy led to the resolution of the schisis cavity 1 year later. This represents the second published account of retinoschisis in the setting of Coats' disease.

FEVR-Like Presentation of Homocystinuria.

A male infant with a diagnosis of homocystinuria presented with avascularity of the peripheral retina with a ridge on ophthalmic exam, consistent with a FEVR-like manifestation homocystinuria. Upon follow-up and treatment for homocystinuria, the retinal vascularity improved without the need for prophylactic treatment to the peripheral avascular retina.

Ocular findings and treatment of a young boy with Coats' plus.

The authors describe a 34-month-old boy who presented with a bilateral and asymmetric exudative retinopathy with similarities to Coats' disease. The patient's medical history was remarkable for hypotonia, developmental delay, seizures, and intracranial calcifications. Genetic testing revealed a diagnosis of Coats' plus. This rare genetic disease should be in the differential diagnosis in patients who present with a bilateral and asymmetric Coats'-like retinopathy in the presence of other systemic abnormalities.

Congenital optic nerve pit in trisomy 18.

The authors report the first case of trisomy 18 associated with a clinically detectable optic nerve pit. A female infant with a birth weight of 2,150 g was born by cesarean section to a healthy 40-year-old woman at 38 weeks of gestation. Trisomy 18 had been diagnosed by prenatal genetic testing. Ophthalmologic examination was remarkable for bilateral narrowed palpebral fissures with punctal agenesis, corectopic pupils without reaction to light, bilateral inferior peripapillary retinochoroidal hypopigmentation, and significant optic nerve cupping in the left eye with associated temporal optic nerve pit. It has generally been accepted that optic nerve pits are a congenital anomaly. However, the pathophysiological background of optic nerve pits remains unclear and controversial. This is the first clinical and photographic documentation of an optic nerve pit in a neonate and in Edwards syndrome.

Familial exudative vitreoretinopathy in a premature child.

Many of the clinical features associated with familial exudative vitreoretinopathy (FEVR) overlap with those commonly found in retinopathy of prematurity (ROP). Differentiating these two distinct entities may be challenging in premature infants. FEVR can be distinguished from ROP in that the former demonstrates exudates on examination and tends to recur or reactivate. The authors report the case of a premature infant diagnosed with FEVR and treated with diode laser who was subsequently lost to follow-up. Upon re-establishing care 3 years later, the patient demonstrated renewed bilateral vitreoretinopathy. This manuscript underscores the importance of accurate distinction between FEVR and ROP for the purpose of optimal patient management.

Congenital optic nerve pit in trisomy 18.

The authors report the first case of trisomy 18 associated with a clinically detectable optic nerve pit. A female infant with a birth weight of 2,150 g was born by cesarean section to a healthy 40-year-old woman at 38 weeks of gestation. Trisomy 18 had been diagnosed by prenatal genetic testing. Ophthalmologic examination was remarkable for bilateral narrowed palpebral fissures with punctal agenesis, corectopic pupils without reaction to light, bilateral inferior peripapillary retinochoroidal hypopigmentation, and significant optic nerve cupping in the left eye with associated temporal optic nerve pit. It has generally been accepted that optic nerve pits are a congenital anomaly. However, the pathophysiological background of optic nerve pits remains unclear and controversial. This is the first clinical and photographic documentation of an optic nerve pit in a neonate and in Edwards syndrome.