Peripheral nonperfusion and tractional retinal detachment associated with congenital optic nerve anomalies.

PURPOSE: To report an association of congenital optic nerve anomalies with peripheral retina nonperfusion and to describe the clinical manifestations and treatment. DESIGN: Retrospective, observational case series. PARTICIPANTS: Fifteen patients with congenital optic nerve anomalies referred for pediatric retina consultation were studied. Sixteen eyes of 9 patients with optic nerve hypoplasia and 8 eyes of 6 patients with other congenital optic nerve anomalies, including optic nerve coloboma, morning glory disc, and peripapillary staphyloma, were included. METHODS: All patients underwent examinations under anesthesia. Wide-angle retina photographs and fluorescein angiograms were reviewed. The severity of nonperfusion was graded. The presence of fibrovascular proliferation (FP), vitreous hemorrhage (VH), and tractional retinal detachment (TRD) were documented. Anatomic outcome after treatment was recorded. MAIN OUTCOME MEASURES: Severity of nonperfusion, occurrence of secondary complications, and the anatomic outcome of patients who underwent laser treatment. RESULTS: In patients with optic nerve hypoplasia, 12 of 16 eyes (75%) had severe peripheral nonperfusion, 12 of 16 eyes (75%) had FP, 3 of 16 eyes (19%) had VH, and 10 of 16 eyes (63%) had TRD. Six of these eyes with severe nonperfusion received laser photocoagulation to the nonperfused retina; laser-treated retinas remained attached in all 6 eyes. In patients with the other optic nerve anomalies, 7 of 8 eyes (88%) had mild to moderate nonperfusion, 2 of 8 eyes (25%) had FP, 1 of 8 eyes (12%) had VH, and 2 of 8 eyes (25%) had TRD. Six of 9 patients (67%) with optic nerve hypoplasia and 1 of 6 patients (17%) with other anomalies had a coexisting congenital brain disease. CONCLUSIONS: Congenital optic nerve anomalies may be associated with peripheral retina nonperfusion and the secondary complications of FP, VH, and TRD. In this select group of patients, the nonperfusion associated with optic nerve hypoplasia seemed to be more severe and associated more frequently with secondary complications. Peripheral retina examination in eyes with optic nerve anomalies may identify nonperfusion or FP. Laser treatment of the avascular retina may have helped prevent complications from proliferative retinopathy in eyes clinically observed to have progressed or considered at risk for progression to proliferative retinopathy.

Presumed Silicone Oil Droplets After Intravitreal Pegcetacoplan Injections.

Importance: Recently, intravitreal pegcetacoplan became the first drug to gain US Food and Drug Administration approval for the treatment of geographic atrophy associated with nonexudative age-related macular degeneration, but the administration of this medication may be associated with unanticipated posttreatment complications. Objective: To assess the prevalence of presumed silicone oil droplets in the vitreous cavity after intravitreal injection of pegcetacoplan. Design, Setting, and Participants: This case series study involved a retrospective record review of all 55 patients treated with intravitreal pegcetacoplan, 0.1 mL in 150-mg/mL solution, between March 24 and June 5, 2023, at a single specialty retina practice. All injections were done using needles from the kit supplied by Apellis Pharmaceuticals on a 1-mL McKesson Luer lock syringe. Main Outcomes and Measures: The presence or absence of presumed silicone bubbles detected during dilated biomicroscopic fundus examination and/or on color fundus photographs, the presence or absence of symptoms, change in visual acuity, and/or increase in intraocular pressure. Results: A total of 62 intravitreal pegcetacoplan injections were given to 55 patients (mean [SD] age, 83.8 [7.8] years; 33 women [60%]) from March 24 to June 5, 2023. Of the 55 patients, 16 (29%; mean [SD] age, 83.8 [7.4] years; 9 women [56%]) had presumed intravitreal silicone droplets discovered 2 to 4 weeks after treatment, 3 of which were documented on color fundus photographs. Of the 16 patients, 14 (88%) were symptomatic for new floaters that they described as persistent, while 2 (13%) were asymptomatic. There were no signs of inflammation or infection, no increases in intraocular pressure, and no changes in visual acuity for all 16 patients. Conclusions and Relevance: A substantial percentage of patients had symptomatic floaters from presumed intravitreal silicone oil droplets after injections of pegcetacoplan using a McKesson 1-mL Luer lock syringe. These findings support consideration of informing patients of this potential adverse effect, avoiding use of the McKesson syringe, and considering use of silicone-free syringes for pegcetacoplan injections.

Visual Acuity, Vitreous Hemorrhage, and Other Ocular Outcomes After Vitrectomy vs Aflibercept for Vitreous Hemorrhage Due to Diabetic Retinopathy: A Secondary Analysis of a Randomized Clinical Trial.

IMPORTANCE: Although there were no differences in mean visual acuity (VA) over 24 weeks after vitrectomy with panretinal photocoagulation (PRP) vs aflibercept in a randomized clinical trial among eyes with vitreous hemorrhage due to proliferative diabetic retinopathy (PDR), post hoc analyses may influence treatment choices. OBJECTIVE: To compare exploratory outcomes between treatment groups that may affect treatment choices for patients with vitreous hemorrhage due to PDR. DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis of a randomized clinical trial conducted at 39 DRCR Retina Network sites included adults with vision loss due to PDR-related vitreous hemorrhage for whom vitrectomy was considered. Data were collected from November 2016 to January 2020. INTERVENTIONS: Random assignment to 4 monthly injections of aflibercept vs vitrectomy with PRP. Both groups could receive aflibercept or vitrectomy during follow-up based on protocol-specific criteria. MAIN OUTCOMES AND MEASURES: Visual acuity area under the curve (adjusted for baseline VA) and clearance of vitreous hemorrhage. RESULTS: A total of 205 eyes were included in the analysis (115 male [56%] and 90 [44%] female participants; mean [SD] age, 57 [11] years). Among 89 eyes with a baseline VA of 20/32 to 20/160 (47 receiving aflibercept, including 4 [9%] that had undergone vitrectomy; 42 undergoing vitrectomy, including 3 [7%] that had received aflibercept), the adjusted mean difference in VA letter score over 24 weeks between the aflibercept and vitrectomy groups was -4.3 (95% CI, -10.6 to 1.9) compared with -16.7 (95% CI, -24.4 to -9.1) among 59 eyes with baseline VA worse than 20/800 (P = .02 for interaction; 26 in the aflibercept group, including 6 [23%] that had undergone vitrectomy; 33 in the vitrectomy group, including 8 [24%] that had received aflibercept). In the full cohort, the median time to clearance of the initial vitreous hemorrhage was 36 (interquartile range [IQR], 24-52) weeks in the aflibercept group vs 4 (IQR, 4-4) weeks in the vitrectomy group (difference, 32 [95% CI, 20-32] weeks; P < .001). CONCLUSIONS AND RELEVANCE: Both initial aflibercept and vitrectomy with PRP are viable treatment approaches for PDR-related vitreous hemorrhage. Although this study did not find a significant difference between groups in the primary outcome of mean VA over 24 weeks of follow-up, eyes receiving initial vitrectomy with PRP had faster recovery of vision over 24 weeks when baseline VA was worse than 20/800 and faster vitreous hemorrhage clearance. Approximately one-third of the eyes in each group received the alternative treatment (aflibercept or vitrectomy with PRP). These factors may influence treatment decisions for patients initiating therapy for PDR-related vitreous hemorrhage. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02858076.

Laser photocoagulation at birth prevents blindness in Norrie's disease diagnosed using amniocentesis.

OBJECTIVE: To report the first case of prophylactic laser treatment to prevent blindness in a patient who was diagnosed with Norrie's disease by genetic testing with amniocentesis. DESIGN: Case report. PARTICIPANTS: A 2-year-old white boy with Norrie's disease. METHODS: A 37-week gestational age male with a family history of Norrie's disease was born via Cesarean section after the mother had undergone prenatal amniocentesis fetal-genetic testing at 23 weeks of gestation. A C520T (nonsense) mutation was found in the Norrie's disease gene. After examination under anesthesia confirmed the diagnosis on the first day of life, laser photocoagulation was applied to the avascular retina bilaterally. The patient was followed closely by ophthalmology, pediatrics, and occupational therapy departments. MAIN OUTCOME MEASURES: Functional outcome, as documented by Teller visual acuity and formal occupational therapy testing, and anatomic outcome, as documented by Retcam photography and fluorescein angiography. RESULTS: Complete regression of extraretinal fibrovascular proliferation was observed 1 month after laser treatment. No retinal detachment had occurred to date at 24 months. Teller visual acuity at 23 months of life was 20/100 in both eyes. The patient's vision and developmental milestones were age appropriate. CONCLUSIONS: Pre-term genetic diagnosis with immediate laser treatment after birth may preserve vision in individuals affected with Norrie's disease.

Clinicopathologic correlation of explanted AlphaCor artificial cornea after exposure of implant.

PURPOSE: To describe the clinical presentation and histopathologic findings in a case of explantation of an AlphaCor artificial cornea implant caused by exposure of the skirt. METHODS: We describe the case report of a 46-year-old man who suffered trauma to the right eye, resulting in 4 failed penetrating keratoplasties (PKPs). Subsequently, an AlphaCor implantation was performed with some visual improvement. Slightly more than 2 years after the implant, skirt exposure occurred, possibly secondary to infectious keratitis in an area of a ruptured bulla, and explantation was performed. Corneal stability was established with repeat corneal transplantation. RESULTS: Histopathologic evaluation of the surgical specimen revealed chronic nongranulomatous inflammation and fibrosis in the peripheral skirt, indicating that biointegration was maintained. However, peripheral corneal stromal melting led to skirt exposure. Focal calcification, as well as retroprosthetic membrane formation, was also identified. CONCLUSIONS: The AlphaCor implant is a viable method of treatment for multiple failed PKPs, but it may be associated with unique complications, including corneal stromal melting, focal calcification, and retroprosthetic membrane formation. Infectious keratitis may be a risk factor for corneal stromal melting and needs to be managed aggressively. Explantation of the implant is essential if the skirt is exposed.

Cross-Sectional Analysis of Neurocognitive Function, Retinopathy, and Retinal Thinning by Spectral-Domain Optical Coherence Tomography in Sickle Cell Patients.

PURPOSE: The purpose was to examine the relationship between neurocognitive function and two distinct forms of retinopathy in sickle cell disease. MATERIALS AND METHODS: Patients with sickle cell disease (n = 44, age range: 19-56 years, 70% female) were prospectively recruited for this cross-sectional study. Retinopathy was characterized by: (1) Presence of focal retinal thinning on spectral domain optical coherence tomography and (2) determination of the sickle retinopathy stage on funduscopic exam based on Goldberg classification. Neurocognitive function was assessed using the Philadelphia Brief Assessment of Cognition (PBAC), a validated test of cognition. Univariate and multivariate analyses for PBAC score outcomes were performed. Retinal thinning and retinopathy stage were primary variables of interest and age, gender, genotype, education, and history of stroke were covariates. RESULTS: Univariate analysis revealed associations with total PBAC score and age (P = 0.049), history of stroke (P = 0.04), and genotype (P < 0.001). Focal retinal thinning and Goldberg retinopathy stage were not associated with each other in this sample. Neither the presence of focal retinal thinning nor degree of retinopathy was associated with total PBAC score in univariate or multivariate analyses. CONCLUSIONS: We find an association between lower cognitive function and older age, history of stroke and sickle cell genotype SS in patients with sickle cell disease. Our data do not provide evidence to support an association between cognitive function and retinopathy in sickle cell patients.

Vitamin A deficiency and xerophthalmic fundus in autoimmune hepatitis and cirrhosis.

PURPOSE: To report a patient with autoimmune hepatitis and cirrhosis who was diagnosed with severe vitamin A deficiency based on the findings of xerophthalmic fundus. METHODS: Retrospective chart review. PATIENT: A 36-year-old African American woman who had a history of autoimmune hepatitis and cirrhosis presents with peripheral retinal white spots, which led to the diagnosis of vitamin A deficiency. RESULTS: The patient presented to the eye clinic for intermittent blurry vision 3 months after the diagnosis of liver cirrhosis secondary to autoimmune hepatitis since age 15. She also underwent partial large and small intestine resection as an infant for Hirschsprung disease. Anterior segment examination was significant for severe punctate epithelial erosions and posterior segment examination was significant for extensive white spots in the peripheral retina in both eyes. Workup showed near nondetectable levels of vitamin A (<0.06 mg/L, normal 0.3-1.2 mg/L) and retinyl palmitate (<0.02 mg/L, normal > 0.2 mg/L). After treatment with 200,000 IU of vitamin A orally, the white spots slowly resolved in ∼6 months. She never developed nyctalopia and her dry eye symptoms completely resolved. CONCLUSION: Although rare, vitamin A deficiency should be considered in patients with liver cirrhosis especially in those with a history of intestinal surgeries. Early diagnosis and treatment with vitamin A supplementation can reverse the signs and symptoms of xerophthalmia.

Treatment of recalcitrant radiation maculopathy using intravitreal dexamethasone (Ozurdex) implant.

PURPOSE: Radiation maculopathy is the most common cause of severe vision loss after radiotherapy of uveal melanoma. To date, no effective therapy exists. The authors report a novel approach to the treatment of radiation maculopathy using dexamethasone (Ozurdex, Allergan Inc) intravitreal implant. METHODS: This is a retrospective case series of two patients who developed radiation maculopathy after radiotherapy for uveal melanoma and was treated with Ozurdex. Clinical outcomes included visual acuity, central foveal thickness by optical coherence tomography, intraocular pressure, and cataract formation. RESULTS: Both patients were of Caucasian descent. Patient 1 received charged-particle radiation, whereas Patient 2 received iodine-125 brachytherapy for medium-sized uveal melanoma located in the midperipheral retina. Radiation maculopathy developed 47 months and 18 months after radiation exposure in Patient 1 and 2, respectively. Both patients initially received bevacizumab monotherapy followed by alternating therapy with bevacizumab and intravitreal triamcinolone. Secondary to a limited response, the patients were treated with Ozurdex implants. One patient had visual improvement, and both patients experienced a prolonged time frame of anatomical stability. Adverse effects included a rise in the intraocular pressure, which was controlled by topical hypotensive agents and posterior subcapsular cataract formation in Patient 1. CONCLUSION: Ozurdex intravitreal implant provides a prolonged period of anatomical stabilization in recalcitrant cases of radiation maculopathy in patients who have failed multiple intravitreal bevacizumab injections and had only a partial response to intravitreal triamcinolone. Larger prospective studies are required to determine the extent of visual benefit.

Peripapillary retinal nerve fiber layer thickness in sickle-cell hemoglobinopathies using spectral-domain optical coherence tomography.

PURPOSE: To determine whether patients with a sickle-cell hemoglobinopathy without glaucoma have peripapillary retinal nerve fiber layer (RNFL) thinning by spectral-domain optical coherence tomography. DESIGN: Prospective study. METHODS: All patients with a sickle cell hemoglobinopathy (sickle-cell disease, sickle-cell hemoglobin C disease, and sickle-cell thalassemia) and age-similar, race-matched controls underwent a comprehensive eye examination and spectral-domain optical coherence tomography of the macula and optic nerve head using the Heidelberg Spectralis (Heidelberg Engineering, Inc, Carlsbad, California, USA). Participants with prior retinal treatments (laser or surgery), diabetes mellitus, glaucoma, or other ocular diseases were excluded. The sickle-cell disease patients were grouped into those with focal macular thinning and those without. Those with macular thinning were grouped further into mild, moderate, and severe thinning groups based on temporal macular thickness. Analysis of variance testing and post hoc analysis with the Tukey test and Pearson correlation were performed to assess for peripapillary RNFL thickness differences among different groups. RESULTS: One hundred fifty-one eyes of 88 sickle-cell patients and 55 eyes of 30 age-similar and race-matched (black) controls were included. Sickle-cell patient eyes with macular thinning (n = 81) had thinner mean peripapillary RNFL thicknesses in the nasal sector (P = .01) compared with non-sickle-cell control eyes and in the superotemporal sector (P = .01) compared with sickle-cell patient eyes without macular thinning (n = 70). In the severe macular thinning subgroup (n = 55), the mean peripapillary RNFL thickness was significantly thinner than that of controls (P < .05) in 6 of 7 sectors. There is a positive linear relationship between temporal macular thickness and global peripapillary RNFL thickness with a Pearson correlation coefficient of 0.60 (P < .0001). CONCLUSIONS: Nonglaucomatous, black sickle-cell patients with focal macular thinning on spectral-domain optical coherence tomography have significantly thinner peripapillary RNFL than those without macular thinning or controls. The degree of thinning correlates with severity of temporal macular thinning. These patients may require different peripapillary RNFL thickness thresholds for future glaucoma evaluations.

Traumatic eye injuries from collapsible wire laundry hampers.

Two patients presented to the University of Illinois at Chicago Eye and Ear Infirmary within 1 year with penetrating eye injuries caused by similar collapsible cloth and wire laundry hampers. Penetrating eye injuries in children are relatively rare but can result in poor visual outcomes and multiple vision-threatening complications. Both injuries at the University of Illinois resulted in an eye laceration as well as retinal complications similar to those reported with a high velocity injury. This now represents a significant pattern of eye injury and suggests that there exists a nontrivial risk for all children in households with this type of collapsible laundry hamper. Parents should receive a warning of the risks of these hampers.

Bilateral traumatic expulsive aniridia after phacoemulsification.

We report a case of bilateral traumatic expulsive aniridia after uneventful phacoemulsification through small clear corneal incisions. Phacoemulsification was performed 8 and 13 months prior to the trauma in the left and right eyes, respectively. In both eyes, the intraocular lens and capsular bag were undisturbed after trauma. After resolution of hyphema, transient elevated intraocular pressure, and anterior chamber inflammation, best corrected visual acuity returned to 20/25 in each eye 6 months later. Self-sealing clear corneal wounds likely serve as a decompression valve during blunt trauma, thus preventing devastating intraocular damage and globe rupture. The intraocular lens may absorb the external force, therefore preventing damage to the capsular bag and zonules as well as preventing prolapse of posterior structures. A review of previously reported cases of traumatic aniridia is also presented.

Lipemia retinalis as a presenting feature of hypertriglyceridemia associated with protease inhibitors in human immunodeficiency virus-infected patients.

PURPOSE: To report two cases of lipemia retinalis in patients infected with human immunodeficiency virus on protease inhibitors with increased triglyceride levels. METHODS: Retrospective review of medical records. Two patients infected with human immunodeficiency virus using protease inhibitors who were diagnosed with severe hypertriglyceridemia based on eye findings of lipemia retinalis. RESULTS: One patient developed triglyceride level of >5,300 mg/dL after adding an integrase inhibitor to a regimen that included protease inhibitors. Hypertriglyceridemia was diagnosed after routine ophthalmic screening for cytomegalovirus retinitis revealed lipemia retinalis. Triglyceride levels improved significantly after both discontinuation of HIV medications and adjustment of cholesterol-lowering medications. Another patient developed triglyceride levels of >9,000 mg/dL while on protease inhibitors, which was also detected on routine retinal examination. Shortly after the diagnosis, he experienced acute coronary syndrome and cardiac arrest requiring plasmapheresis and emergent bypass surgery. CONCLUSION: Lipemia retinalis is rare but may be a presenting sign of severe hypertriglyceridemia in patients infected with human immunodeficiency virus. Recognition of this condition during the ophthalmic examination can lead to diagnosis and may allow for treatment before the development of life-threatening complications, such as pancreatitis and acute coronary syndrome.

Use of infliximab in the treatment of peripheral ulcerative keratitis in Crohn disease.

PURPOSE: To report the effectiveness of infliximab in the treatment of peripheral ulcerative keratitis (PUK) associated with Crohn disease. DESIGN: Retrospective, interventional case series. SETTING: Institutional, academic referral setting. patient or study population: Six eyes of 3 patients with PUK associated with Crohn disease that failed or were intolerant to traditional immunosuppression such as oral prednisone and cyclophosphamide. INTERVENTION OR OBSERVATION PROCEDURE(S): Infliximab intravenous infusion 5 mg/kg every 2 to 8 weeks. MAIN OUTCOME MEASURE(S): Subjective outcome such as pain improvement and objective outcomes such as visual acuity, signs of inflammation, and progression of corneal thinning. RESULTS: Symptom of pain improved in all patients. Visual acuity remained stable in 4 of 6 eyes, improved in 1 of 6 eyes, and worsened in 1 of 6 eyes (secondary to stromal scar). Rapid resolution of inflammation and arrest of further thinning were observed in all 6 eyes. Similar effects were observed on recurrence treated with repeat dosing of infliximab in 5 of 6 eyes. CONCLUSIONS: Infliximab produced a rapid, dramatic, repeatable suppression of corneal inflammation, pain, and keratolysis in PUK associated with Crohn disease. Although the effect of long-term therapy with these agents is unknown, infliximab should be considered in patients with Crohn-associated PUK not amenable to traditional therapy. Larger prospective studies are needed to determine the efficacy of infliximab in this aggressive disease entity.

Structural and functional correlation in sickle cell retinopathy using spectral-domain optical coherence tomography and scanning laser ophthalmoscope microperimetry.

PURPOSE: To correlate macular structural changes by spectral-domain optical coherence tomography (SD-OCT) with functional changes by scanning laser ophthalmoscope (SLO) microperimetry testing in patients with sickle cell hemoglobinopathies. DESIGN: Prospective, investigational study. METHODS: Patients with electrophoretic confirmation of sickle cell hemoglobinopathies and normal subjects underwent SD-OCT and microperimetry testing with the OPKO Spectral OCT/SLO instrument. Based on SD-OCT findings, patients were grouped into those with focal macular thinning (Group A) and those without (Group B). Main outcome measure were mean retinal sensitivities measured by microperimetry and mean macular thicknesses in the 9 Early Treatment Diabetic Retinopathy Study (ETDRS)-like subfields. RESULTS: Thirty-seven eyes of 19 patients with sickle cell hemoglobinopathies (SS, SC, and S-thalassemia) and 34 eyes of 34 age-similar normal controls were included. Mean age and mean logMAR best-corrected visual acuity between Groups A and B were not statistically different (39.7 years vs 36.5 years, P = .64 and 0.015 vs 0.016, P = .93, respectively). Group A had significantly thinner retinas compared to Group B in the parafoveal superior (P = .019), parafoveal temporal (P < .004), parafoveal inferior (P = .003), perifoveal superior (P = .04), perifoveal temporal (P = .0005), and perifoveal inferior (P = .045) subfields. The overall mean microperimetry retinal sensitivities of Group A were significantly less than those of Group B (14.2 dB vs 16.5 dB, P = .00005). However, there was no statistical difference between Group B and controls (16.5 dB vs 16.7 dB, P = .63). CONCLUSION: Sickle cell patients with focal macular thinning present on SD-OCT have significantly decreased retinal sensitivities compared to those without focal thinning or normal controls based on mean microperimetry sensitivities, despite similar age and visual acuity. Microperimetry is a sensitive measurement of macular function in patients with sickle cell hemoglobinopathies.

Effects of green diode laser in the treatment of pediatric Coats disease.

PURPOSE: To review the effect of green diode laser ablation therapy on retinal structure and functional outcome in patients with advanced Coats disease. DESIGN: Retrospective, interventional case series. METHODS: Fourteen eyes of 13 patients with Coats disease were included in this study. Medical records, Retcam photographs (Clarity Medical Systems, Pleasanton, CA), and fluorescein angiograms were reviewed. All patients initially were treated with green diode laser (532 nm) ablation therapy to areas of the retinal telangiectasis associated with exudation. Main outcome measures included visual acuity, treatment outcome defined as complete resolution of telangiectatic lesions or exudative detachment, and macular status at the end of follow-up. RESULTS: Before treatment, 1 eye was at stage 2 (telangiectasis and exudation), 12 eyes were at stage 3 (exudative retinal detachment), and 1 eye was at stage 4 (total retinal detachment with glaucoma). Five eyes had highly detached retina of more than 4 mm. Median age at diagnosis was 51 months (range, 0.5 to 153 months). Median follow-up was 39.5 months (range, 15 to 70 months). Median number of green diode laser photocoagulation treatments was 2 (range, 1 to 5). After laser photocoagulation, 13 (93%) of 14 eyes had no active exudation. Functionally, 4 (29%) of 14 eyes had 20/50 or better visual acuity, 3 (21%) of 14 eyes had 20/60 to 20/200 visual acuity, 5 (36%) of 14 eyes had 20/400 to light perception visual acuity, and 2 (14%) of 14 eyes had no light perception visual acuity. No eye was phthisical or enucleated. CONCLUSIONS: Green diode laser therapy can be an effective treatment for advanced Coats disease, even in the presence of a moderate to severely elevated retinal detachment.

Septo-optic dysplasia with bilateral congenital corneal anesthesia.

Septo-optic dysplasia, or de Morsier syndrome, is characterized by optic nerve hypoplasia with an absent septum pellucidum and/or pituitary abnormalities. Congenital corneal anesthesia is a rare disorder that has been associated with many neurological disorders. Here we present a patient with both conditions who was successfully treated with permanent lateral tarsorrhaphy and aggressive lubrication. To our knowledge, congenital corneal anesthesia has not been reported in association with septo-optic dysplasia. The purpose of this report is to make pediatric ophthalmologists aware of a potential association since the diagnosis of congenital corneal anesthesia is often difficult and delayed.

1 alpha-Hydroxyvitamin D2 inhibits growth of human neuroblastoma.

Neuroblastoma is the most common extracranial solid tumor in childhood. The poor outcomes of patients with high-risk neuroblastoma have encouraged the search for new therapies. In the current study, the effect of the vitamin D analog 1alpha-hydroxyvitamin D2 (1alpha-OH-D2, doxercalciferol) was assessed in a mouse xenograft model of human neuroblastoma. Vitamin D receptor (VDR) expression levels in seven neuroblastoma cell lines were compared using real-time PCR. SK-N-AS cells, which express relatively high levels of VDR, were injected into the flanks of 60 mice. The mice were treated daily via oral gavage for 5 weeks with vehicle (control), 0.15 microg, or 0.3 microg of 1alpha-OH-D2. The animals were then euthanized, and tumors, sera, and kidneys were collected and analyzed. End tumor volumes were significantly smaller in both the 0.15 microg group (712.07 mm3, P = 0.0121) and 0.3 microg group (772.97 mm3, P = 0.0209) when compared to controls (1,681.75 mm3). In terms of toxicity, serum calcium levels were increased but mortality was minimal in both treatment groups. These results were similar to those previously described in the transgenic (LHbeta-Tag) and human xenograft (Y-79) models of retinoblastoma, a related tumor. In vitro cell viability studies of SK-N-AS and NGP cells, which represent two major human neuroblastoma subtypes that differ in their genetic abnormalities as well as their VDR expression levels, show that both are sensitive to calcitriol, the active metabolite of vitamin D3. In conclusion, the present study shows that 1alpha-OH-D2 can inhibit human neuroblastoma growth in vivo with relatively low toxicity. The safety of 1alpha-OH-D2 has been extensively studied; the drug is FDA-approved for the treatment of adult kidney patients, and Phase I/II trials have been conducted in adult oncology patients. There should not be major obstacles to starting Phase I and II clinical trials with this drug in pediatric patients with high-risk neuroblastoma.

Chain length dependence of apomyoglobin folding: structural evolution from misfolded sheets to native helices.

Very little is known about how protein structure evolves during the polypeptide chain elongation that accompanies cotranslational protein folding. This in vitro model study is aimed at probing how conformational space evolves for purified N-terminal polypeptides of increasing length. These peptides are derived from the sequence of an all-alpha-helical single domain protein, Sperm whale apomyoglobin (apoMb). Even at short chain lengths, ordered structure is found. The nature of this structure is strongly chain length dependent. At relatively short lengths, a predominantly non-native beta-sheet conformation is present, and self-associated amyloid-like species are generated. As chain length increases, alpha-helix progressively takes over, and it replaces the beta-strand. The observed trends correlate with the specific fraction of solvent-accessible nonpolar surface area present at different chain lengths. The C-terminal portion of the chain plays an important role by promoting a large and cooperative overall increase in helical content and by consolidating the monomeric association state of the full-length protein. Thus, a native-like energy landscape develops late during apoMb chain elongation. This effect may provide an important driving force for chain expulsion from the ribosome and promote nearly-posttranslational folding of single domain proteins in the cell. Nature has been able to overcome the above intrinsic misfolding trends by modulating the composition of the intracellular environment. An imbalance or improper functioning by the above modulating factors during translation may play a role in misfolding-driven intracellular disorders.