Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP): 12-month experience with telemedicine screening.

BACKGROUND/AIMS: To report the 1-year experience of the Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) telemedicine initiative. METHODS: Forty-two consecutively enrolled infants who met ROP examination criteria were screened between 1 December 2005 through 30 November 2006 with the RetCam II and evaluated by the SUNDROP reading centre at Stanford University. Nurses obtained five images in each eye. All patients also received a dilated examination by the author within 1 week of discharge from the hospital. Outcomes included referral-warranted disease, need for treatment and anatomical outcomes. Referral-warranted disease was defined as any Early Treatment Retinopathy of Prematurity (ROP) Disease Type 2 or greater, or any plus disease. A retrospective analysis of 84 eyes, 131 unique examinations and 1315 unique images from the SUNDROP archival data is reported here. RESULTS: In the initial 12-month period, the SUNDROP telemedicine screening initiative had not missed any referral warranted ROP. Calculated sensitivity and specificity was 100% and 95%, respectively. No patient progressed to retinal detachment or other adverse outcomes. CONCLUSIONS: The SUNDROP telemedicine screening initiative for ROP has proven to have a high degree of sensitivity and specificity for identification of referral warranted disease. These results indicate that telemedicine may improve accessibility of ROP screening.

Retinopathy of prematurity in the United States.

AIMS: To determine the incidence of retinopathy of prematurity (ROP) based upon a national database and to identify baseline characteristics, demographic information, comorbidities, and surgical interventions. METHODS: The National Inpatient Sample, a representative sample of all US hospital discharges from 1997 to 2002, was queried for all newborn infants with and without ROP. Primary outcome variables included demographics, comorbidities, hospital length of stay (LOS), and hospital charges. Multivariate logistic regression was used to predict risk factors for ROP. RESULTS: 4.67 million live births were recorded during the study period. The total incidence of ROP was 0.12% overall and 7.35% for premature infants with LOS greater than 14 days. Newborns with ROP were more likely to be born at a teaching hospital and to have higher LOS and hospitalisation charges. The odds ratios for the development of ROP were greatest in infants weighing less than 1250 grams. The multivariate regression model revealed that only respiratory distress and intraventricular haemorrhage were predictive of the development of ROP and Hispanic infants were 33% more likely to develop ROP. CONCLUSION: This study represents the largest cohort of newborns analysed for ROP. The multivariate analysis emphasised the role of birth weight in extended-stay infants, as well as Hispanic race, respiratory distress syndrome, and intraventricular haemorrhage.

Severe surfing-related ocular injuries: the Stanford Northern Californian experience.

There is a growing body of literature describing severe surfing-related ocular injuries that result in permanent vision loss. We describe three severe surfing-related ocular injuries that occurred on beaches in northern California. One particular case stresses the need to tailor treatment to the patient and injury because of the possibility of good outcomes despite severe injury. Attention should also be directed towards commercially available safety gear and providing additional safety measures to prevent other orbital and ocular injuries.

Splice site mutation in the peripherin/RDS gene associated with pattern dystrophy of the retina.

PURPOSE: To report the phenotype and genotype of a splice site mutation at intron 2 of the peripherin/RDS gene in four half-siblings with pattern dystrophy of the retina. DESIGN: Experimental study. METHODS: In four siblings with a common mother and three separate fathers, complete ophthalmic examination, pedigree, electrophysiologic testing, and fluorescein angiography studies were obtained. Genomic DNA from serum lymphocytes was isolated and used as a template for primers specific for the cone homeobox gene (CRX), rhodopsin (RHO), and peripherin/RDS genes to conduct single stranded conformational analysis and cycle sequencing. RESULTS: The pedigree of four affected siblings suggested probable autosomal dominance transmission of pattern dystrophy. In the four siblings, best corrected visual acuity ranged from 20/20 to 20/80 by Snellen chart. Clinical findings included discrete, localized degenerative changes of the macular retinal pigment epithelium in all patients, with subclassification foveal. One patient exhibited pigment clumping within the atrophic areas. Another patient exhibited yellow flecks diffusely in the macula. Fluorescein angiographic findings included central hypofluorescence with a surrounding rim of hyperfluorescence that corresponded to the observed fundus lesions and window defects. There was a range of electroretinography (ERG) and electrooculography (EOG) findings. One patient demonstrated both cone and rod dysfunction on ERG testing and another demonstrated decreased rod function. EOG testing was normal in two patients and mildly diminished in one patient. DNA sequencing identified a point mutation in intron 2 of the peripherin/RDS gene, consisting of an A to T change at 1068+3, present in all four affected patients. CONCLUSIONS: Four siblings with pattern dystrophy of the retina presented a splice site mutation in the peripherin/RDS gene.

Multiagent chemotherapy as neoadjuvant treatment for multifocal intraocular retinoblastoma.

PURPOSE: To evaluate the efficacy of multiagent chemotherapy in the neoadjuvant treatment of retinoblastoma. DESIGN: Noncomparative, prospective case series. PARTICIPANTS: Twenty consecutive patients with multifocal intraocular retinoblastoma (4 unilateral, 16 bilateral [36 eyes]). INTERVENTION: Eight cycles of chemotherapy with carboplatin and vincristine were administered at 3-week intervals over a 6-month period. Supplemental therapy was withheld until disease progression was documented. MAIN OUTCOME MEASURES: Disease progression (defined as tumor growth, vitreous or subretinal seed progression, and new tumor formation), delay of external beam radiotherapy, and ocular survival. RESULTS: Thirty-six eyes were treated. Eighteen eyes had Reese-Ellsworth group I-III tumors, and 16 eyes had Reese-Ellsworth group IV-V tumors at diagnosis. Two patients, who had unilateral disease at diagnosis, subsequently had tumors develop in the contralateral eye. Nineteen of 20 patients (95%) completed eight cycles of chemotherapy without disease progression. Three eyes of three different patients were successfully treated with chemotherapy alone. Thirty-three of 36 eyes (92%) progressed after completion of chemotherapy: 15 of the 18 eyes (83.3%) with Reese-Ellsworth group I-III and 16 of 16 eyes (100%) with Reese-Ellsworth group IV-V tumors. Seventeen eyes (52%) had growth of a tumor, whereas 14 eyes (42%) had progressive vitreous seeding, and 2 eyes (6%) had new tumors develop. Fifteen eyes (42%) required external beam radiotherapy. Twenty-nine of 36 (80.5%) eyes were salvaged. The median follow-up after chemotherapy was 19 months (range, 3-42 months). CONCLUSIONS: Multiagent chemotherapy alone does not ensure a cure for multifocal intraocular retinoblastoma. Supplemental focal therapy is needed to control disease progression.

Retreatment effect of NPe6 photodynamic therapy on the normal primate macula.

PURPOSE: To evaluate the safety and efficacy of repeated photodynamic therapy (PDT) with mono-L-aspartyl chlorin e6 (NPe6) on normal primate fovea and choroid. METHODS: Macaca fuscata monkeys were used as experimental subjects. Mono-L-aspartyl chlorin e6 at a dose of 2 mg/kg was administered by intravenous infusion. Laser irradiation was applied within 5 minutes using a 664-nm diode laser at a power output of 5.9 mW (750 mW/cm2), spot size of 1,000 microm, and time of 10 seconds. This resulted in a fluence of 7.5 J/cm2. Three consecutive PDT treatments at 2-week intervals were applied over the center of the fovea and posterior fundus near the arcade vessels of each eye. The animals were killed and the eyes were enucleated for histologic study 2 weeks after the last treatment. RESULTS: Limited changes could be observed in the sensory retina under light microscopy. Photoreceptor cells and outer segments were not damaged, even after repeated PDT. Proliferation and duplication of the retinal pigment epithelial cells were common findings. A plaque of fibrous tissue was present, interwoven with retinal pigment epithelial cells in eyes that received repeated PDT. The retinal vessels remained patent even after three sessions of PDT. However, occlusion of the choriocapillaris and the large choroidal vessels was observed after repeated PDT treatment. CONCLUSION: Repeated PDT of healthy nonhuman primate fundi using a hydrophilic photosensitizer (NPe6) shows preservation of the neurosensory retina components and architecture with damage confined to the retinal pigment epithelium and choriocapillaris.

Photodynamic therapy of experimental choroidal neovascularization with a hydrophilic photosensitizer: mono-L-aspartyl chlorin e6.

PURPOSE: To demonstrate the selective localization of the hydrophilic photosensitizer mono-L-aspartyl chlorin e6 (NPe6) in experimental choroidal neovascularization in nonhuman primate eyes. METHODS: Sixty-seven experimental choroidal neovascular lesions (CNV) were created in the fundi of Macaca monkeys using the modified Ryan's model and documented by fluorescein and indocyanine green angiography. To determine the biodistribution of NPe6 and the optimal timing of laser irradiation after dye administration, NPe6 angiography and fluorescence microscopy with NPe6 were performed. Photodynamic therapy (PDT) was performed at various dye doses (0.5-10.0 mg/kg) and laser fluences (7.5-225.0 J/cm2) on the CNV and on 10 areas of normal retina and choroid. Treatment outcomes were assessed by fluorescein and indocyanine green angiography and confirmed by light and electron microscopy. RESULTS: NPe6 fluorescence microscopy demonstrated intense fluorescence of CNV and retinal pigment epithelial cells. Choroidal vessel walls and outer retina adjacent to CNV fluoresced moderately; retinal vessel walls and microcapillaries had trace fluorescence. The fluorescence of CNV lesions on fluorescein angiography became stronger than that of retinal vessels 20-60 minutes after dye injection. Choroidal neovascular lesion closure was achieved with NPe6 PDT without significant damage to the sensory retina. Histology demonstrated necrosis of CNV endothelial cells with minimal damage to surrounding tissues. CONCLUSIONS: NPe6 PDT selectively localizes to experimental CNV in nonhuman primates, resulting in occlusion of CNV with sparing of the neurosensory retina.

Toxicity of the photosensitizer NPe6 following intravitreal injection.

BACKGROUND AND OBJECTIVE: To determine the retinal toxicity of mono-L-aspartyl chlorin e6 (NPe6) following intravitreal injection. METHODS: Twelve Dutch-belted rabbits divided into 5 experimental groups (n=2 each) were injected intravitreally with 6.25, 12.5, 25, 50, or 100 microg of NPe6; one control group (n=2) was injected with intravitreal normal saline. One eye in each rabbit was sutured shut to test the effect of light exposure. Fundus photography and electroretinograms were performed before treatment and 2 days, 1 week, and 2 weeks after injection. Animals were euthanized and the eyes enucleated for histopathologic analysis. RESULTS: After 1 week, 4 uncovered eyes given 50 and 100 microg had central retinal vein occlusion and varying degrees of retinal hemorrhage. RPE proliferation was seen in the covered eyes given 50 or 100 microg. Electroretinograms revealed absent retinal response at 100 microg and mild toxicity at 50 microg, but no change from normal at doses of < or = 25 microg of NPe6. CONCLUSIONS: Intravitreal doses of < or = 25 microg NPe6 caused little or no apparent toxicity; however, toxicity was significant at doses of 50 microg and 100 microg.

Mardi Gras eye injury survey, 1998-1999.

BACKGROUND: We studied the nature of associated ocular trauma during the 1998 and 1999 New Orleans parade seasons and whether trends were observable from previous surveys. METHODS: A prospective survey and retrospective analysis included 18 emergency rooms (ERs) in the New Orleans area. RESULTS: Sixteen surveys representing eight ERs were completed between February 19 and 24, 1998, and 32 surveys representing five ERs were completed between February 5 and 17, 1999. In both years, the most common ocular complaints were pain, blur, foreign body sensation, tearing, and photophobia. The most common slit lamp findings in 1998 were within normal limits, corneal abrasion, and conjunctival hyperemia. In 1999, the most common findings were subconjunctival hemorrhage, corneal abrasion, cell and flare, and lid laceration. CONCLUSIONS: Projectile injuries of the eyes are common during Mardi Gras due to the nature of interaction between paradegoers and float riders. We found no identifiable trend in the number or type of injuries reported in 1986, 1987, and 1998 Mardi Gras surveys.

Enucleation.

The three most common indications for enucleation are intraocular malignancy, trauma, and a blind, painful eye. Recommending enucleation is one of the most difficult therapeutic decisions in ophthalmology. In some cases of malignancy, cryotherapy, laser photocoagulation, diathermy, chemotherapy, and radiation therapy may be viable alternatives to surgery. When surgery is chosen, evisceration or exenteration may be alternatives to enucleation. Once the decision is made to perform enucleation or evisceration, the surgeon must choose from several types of implants and wrapping materials. These devices can be synthetic, autologous, or eye-banked tissues. With certain implants, the surgeon must decide when and if to drill for subsequent peg placement. In this review, the authors discuss choices, techniques, complications, and patient consent and follow-up before, during, and after enucleation. Controversies and results of the Controlled Ocular Melanoma Study are summarized.

Problems with and pitfalls of photodynamic therapy.

OBJECTIVE: To delineate the various factors that may influence the outcome of photodynamic therapy of the retina and choroid. DESIGN: Experimental animal study. ANIMALS: Pigmented and nonpigmented rabbits; rhesus monkeys. INTERVENTION: The hydrophilic photosensitizer, mono-L-aspartyl chlorin e6, which is maximally activated at 664 nm, was studied after intravenous injection into pigmented and nonpigmented rabbits and rhesus monkeys. Laser light was supplied by a red diode laser coupled to a modified slit-lamp biomicroscope and delivered to the ocular fundus after passing through a standard fundus contact lens. Standard photodynamic parameters were used. The effects of fundus pigmentation, intraocular pressure, spot focus and defocus, region of fundus treated, equivalent fluence, and retreatment were observed in the different animal species. MAIN OUTCOME MEASURES: Slit-lamp biomicroscopy, fluorescein angiography, light and transmission electron microscopy. RESULTS: Fundus pigmentation appeared to be a factor only at the lowest fluence level tested, where only 4 of 12 lesions attempted in pigmented fundi were noted on fluorescein angiography, compared with 12 of 12 lesions in albino rabbits. At normal intraocular pressures and a given fluence, 10 of 10 lesions were fully manifested on fluorescein angiography, compared with 4 of 10 at 30 mmHg and 0 of 10 at pressures sufficient to blanch the optic nerve (>60 mmHg). For laser spots either focused or defocused, there were 6 of 6 lesions that were fully manifested on fluorescein angiography for each of the parameters. Lesions treated in the fovea resulted in larger spots on fluorescein angiography. The fluence of 5 mW for 10 seconds resulted in a larger lesion on angiography than the equivalent fluence of 10 mW for 5 seconds. Areas of retreatment in rabbits demonstrated more thinning of the neurosensory retina and loss of photoreceptor outer segments and nuclei than corresponding areas receiving one treatment. CONCLUSIONS: Photodynamic therapy results varied, depending on intraocular pressure, region of fundus treated, ocular pigmentation, and the total time of exposure to the photosensitizer. Retreatment resulted in progressive thinning of the neurosensory retina with loss of photoreceptor outer segments and nuclei in the rabbit eye.

Angiographic and histologic effects of fundus photodynamic therapy with a hydrophilic sensitizer (mono-L-aspartyl chlorin e6).

PURPOSE: To demonstrate the efficacy of the photosensitizer mono-L-aspartyl chlorin e6 (NPe6) in closing choroidal vessels at low energy levels, that tissue uptake and clearance are rapid, and that low concentrations of drug are needed to achieve clinical effects. DESIGN: Experimental animal study. ANIMALS: Pigmented rabbits and Japanese monkeys were used in this study. METHODS: Using a modified 664-nm diode laser, the fundi of pigmented rabbits and Japanese monkeys were irradiated after intravenous administration of NPe6 (2-100 mg/kg). Time from injection to irradiation varied from 5 to 15 minutes, and duration of exposure varied from 1 to 10 seconds. Power output at the corneal surface was either 3.6 or 5.9 mW. Animals were examined by indirect ophthalmoscopy and fluorescein angiography at 2 hours and 7 days after treatment. After enucleation 7 days after treatment, specimens were prepared for light and electron microscopy. MAIN OUTCOME MEASURES: Angiographic evidence of occlusion and histopathologic evidence of retinal damage. RESULTS: Both clinical and histopathologic examination demonstrated effects on the choroidal vasculature and the retinal pigment epithelium, including necrosis of endothelial cells and occlusion in choroidal vessels, particularly within the choriocapillaris, at low energy levels. Overlying neurosensory retina was minimally affected. Fluorescein angiography of lesions treated with 2 mg/kg and laser fluence of 2.3 to 7.5 J/cm2 showed a normal appearance 2 hours after treatment, which changed to early hypofluorescent and later hyperfluorescent lesions 7 days after treatment. In contrast, those animals receiving the 10-mg/kg dose and laser fluence of 0.46 to 0.75 J/cm2 showed marked hypofluorescence of choroidal lesions and occlusion of retinal vessels 7 days after treatment. CONCLUSIONS: Effective occlusion of normal choroidal vessels was achieved at 2 mg/kg using 2.3 to 7.5 J/cm2 or at 10 mg/kg using 0.46 to 0.75 J/cm2 with minimal injury to overlying neurosensory retina.

Ocular vascular thrombosis following tin ethyl etiopurpurin (SnET2) photodynamic therapy: time dependencies.

BACKGROUND AND OBJECTIVES: To evaluate the optimal time from the end of photosensitizer injection to the commencement of light application for creating characteristic fundus lesions and the time to vascular occlusion following photodynamic therapy (PDT) with tin ethyl etiopurpurin (SnET2). MATERIALS AND METHODS: Following intravenous injection of SnET2 0.5 mg/kg or lipid emulsion alone, the fundus of rabbits was irradiated at different times (5 to 240 minutes) after photosensitizer injection using 664 +/- 7-nm laser light with an irradiance of 354 mW/cm2 and fluence of 20 J/cm2. Ophthalmoscopy and fluorescein angiography were performed 1 day after SnET2 PDT. In separate groups of rabbits, treated areas of the fundus were imaged within 30 minutes following PDT using fluorescein vesicle and microsphere angiography with scanning laser ophthalmoscopy to document time of vascular occlusion. All animals were killed 1 day following treatment and eyes were examined by histopathology. RESULTS: Areas of hypofluorescence (indicating vascular occlusion) were seen when activating laser light was applied 5 to 20 minutes after SnET2 injection. Retinal vessels remained perfused in all cases. The time to vascular occlusion was 70 to 120 and 40 to 90 minutes in nonpigmented and pigmented rabbits, respectively. No safety issues were seen. CONCLUSION: PDT with SnET2 was effective in occluding the choriocapillaris. Activating light needs to be applied within a specific time frame after photosensitizer injection to achieve vascular occlusion.