The Prevalence of Retinal Disease and Associated CNS Disease in Young Patients with Incontinentia Pigmenti.

PURPOSE: To evaluate the prevalence of retinal disease on fluorescein angiography (FA) in patients with incontinentia pigmenti (IP) and to compare the severity of retinal disease in those with and without known central nervous system (CNS) disease. DESIGN: Multi-institutional consecutive retrospective case series. SUBJECTS: New patients with a diagnosis of IP were seen at the Casey Eye Institute at the Oregon Health and Science University (OHSU), Moran Eye Center, University of Utah, or Bascom Palmer Eye Institute, University of Miami from December 2011 to September 2018. METHODS: Detailed ophthalmoscopic examination and FA were recommended for all new patients and performed on every patient who had parental consent. Ophthalmoscopic findings and FA images were graded for severity by 2 masked graders on a 3-point scale: 0 = no disease, 1 = vascular abnormalities without leakage, 2 = leakage or neovascularization, and 3 = retinal detachment. The presence of known CNS disease was documented. Additional cases were obtained from a pediatric retina listserv for examples of phenotypic variation. MAIN OUTCOME MEASURES: The proportion of eyes noted to have disease on ophthalmoscopy compared with FA and the severity of retinal disease in those with and without known CNS disease. RESULTS: Retinal pathology was detected in 18 of 35 patients (51%) by indirect ophthalmoscopy and 26 of 35 patients (74%) by FA (P = 0.048) in a predominantly pediatric population (median age, 9 months). Ten patients (29%) had known CNS disease at the time of the eye examination. A Wilcoxon rank-sum test indicated that the retinal severity scores for patients with CNS disease (median, 2) were significantly higher than the retinal severity scores for patients without CNS disease (median, 1), z = -2.12, P = 0.034. CONCLUSIONS: Retinal disease is present in the majority of patients with IP, and ophthalmoscopic examination is less sensitive than FA for detection of disease. There may be a correlation between the severity of retinal and CNS disease.

Traumatic Retinal Detachment in Patients with Self-Injurious Behavior: An International Multicenter Study.

PURPOSE: To describe the clinical characteristics, surgical outcomes, and management recommendations in patients with traumatic rhegmatogenous retinal detachment (RRD) resulting from self-injurious behavior (SIB). DESIGN: International, multicenter, retrospective, interventional case series. PARTICIPANTS: Patients with SIB from 23 centers with RRD in at least 1 eye. METHODS: Clinical histories, preoperative assessment, surgical details, postoperative management, behavioral intervention, and follow-up examination findings were reviewed. MAIN OUTCOME MEASURES: The rate of single-surgery anatomic success (SSAS) was the primary outcome. Other outcomes included new RRD in formerly attached eyes, final retinal reattachment, and final visual acuity. RESULTS: One hundred seven eyes with RRDs were included from 78 patients. Fifty-four percent of patients had bilateral RRD or phthisis bulbi in the fellow eye at final follow-up. The most common systemic diagnoses were autism spectrum disorder (35.9%) and trisomy 21 (21.8%) and the most common behavior was face hitting (74.4%). The average follow-up time was 3.3 ± 2.8 years, and surgical outcomes for operable eyes were restricted to patients with at least 3 months of follow-up (81 eyes). Primary initial surgeries were vitrectomy alone (33.3%), primary scleral buckle (SB; 26.9%), and vitrectomy with SB (39.7%), and 5 prophylactic SBs were placed. Twenty-three eyes (21.5%) with RRDs were inoperable. The SSAS was 23.1% without tamponade (37.2% if including silicone oil), and final reattachment was attained in 80% (36.3% without silicone oil tamponade). Funnel-configured RRD (P = 0.006) and the presence of grade C proliferative vitreoretinopathy (P = 0.002) correlated with re-detachment. The use of an SB predicted the final attachment rate during the initial surgery (P = 0.005) or at any surgery (P = 0.008. These associations held if restricting to 64 patients with ≥12 months followup. Anatomic reattachment correlated with better visual acuity (P < 0.001). CONCLUSIONS: RRD resulting from SIB poses therapeutic challenges because of limited patient cooperation, bilateral involvement, chronicity, and ongoing trauma in vulnerable and neglected patients. The surgical success rates were some of the lowest in the modern retinal detachment literature. The use of an SB may result in better outcomes, and visual function can be restored in some patients.

RNA interference targeting hypoxia-inducible factor 1α via a novel multifunctional surfactant attenuates glioma growth in an intracranial mouse model.

OBJECT: High-grade gliomas are the most common form of adult brain cancer, and patients have a dismal survival rate despite aggressive therapeutic measures. Intratumoral hypoxia is thought to be a main contributor to tumorigenesis and angiogenesis of these tumors. Because hypoxia-inducible factor 1α (HIF-1α) is the major mediator of hypoxia-regulated cellular control, inhibition of this transcription factor may reduce glioblastoma growth. METHODS: Using an orthotopic mouse model with U87-LucNeo cells, the authors used RNA interference to knock down HIF-1α in vivo. The small interfering RNA (siRNA) was packaged using a novel multifunctional surfactant, 1-(aminoethyl) iminobis[N-(oleicylcysteinylhistinyl-1-aminoethyl)propionamide] (EHCO), a nucleic acid carrier that facilitates cellular uptake and intracellular release of siRNA. Stereotactic injection was used to deliver siRNA locally through a guide-screw system, and delivery/uptake was verified by imaging of fluorescently labeled siRNA. Osmotic pumps were used for extended siRNA delivery to model a commonly used human intracranial drug-delivery technique, convection-enhanced delivery. RESULTS: Mice receiving daily siRNA injections targeting HIF-1α had a 79% lower tumor volume after 50 days of treatment than the controls. Levels of the HIF-1 transcriptional targets vascular endothelial growth factor (VEGF), glucose transporter 1 (GLUT-1), c-MET, and carbonic anhydrase-IX (CA-IX) and markers for cell growth (MIB-1 and microvascular density) were also significantly lower. Altering the carrier EHCO by adding polyethylene glycol significantly increased the efficacy of drug delivery and subsequent survival. CONCLUSIONS: Treating glioblastoma with siRNA targeting HIF-1α in vivo can significantly reduce tumor growth and increase survival in an intracranial mouse model, a finding that has direct clinical implications.

Light transmittance of 1-piece hydrophobic acrylic intraocular lenses with surface light scattering removed from cadaver eyes.

PURPOSE: To assess the potential effect of surface light scattering on light transmittance of 1-piece hydrophobic acrylic intraocular lenses (IOLs) with or without a blue-light filter. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. DESIGN: Experimental study. METHODS: Intraocular lenses were obtained from human cadavers (49 IOLs total; 36 with blue-light filter) and from finished-goods inventory (controls). The IOLs were removed from cadaver eyes and the power and model matched to unused controls. After surface proteins were removed, the IOLs were hydrated for 24 hours at room temperature. Surface light scattering was measured with a Scheimpflug camera (EAS-1000 Anterior Segment Analysis System). Light transmittance was measured with a Lambda 35 UV/Vis spectrophotometer (single-beam configuration; RSA-PE-20 integrating sphere). RESULTS: Hydrated scatter values ranged from 4.8 to 202.5 computer-compatible tape (CCT) units for explanted IOLs with blue-light filter and 1.5 to 11.8 CCT units for controls; values ranged from 6.0 to 137.5 CCT units for explanted IOLs without a blue-light filter and 3.5 to 9.6 CCT units for controls. In both groups, there was a tendency toward increasing scatter values with increasing postoperative time. No differences in light transmittance were observed between explanted IOLs and controls in both groups (IOLs with blue-light filter: P=.407; IOL with no blue-light filter: P=.487; both paired t test). CONCLUSIONS: Although surface light scattering of explanted IOLs was significantly higher than that of controls and appeared to increase with time, no effect was observed on light transmittance of 1-piece hydrophobic acrylic IOLs with or without a blue-light filter.

Capsular bag opacification with a new accommodating intraocular lens.

PURPOSE: To evaluate the biocompatibility and capsular bag opacification of an accommodating intraocular lens (IOL) containing large haptic elements that separate the anterior and posterior capsules. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. DESIGN: Experimental study. METHODS: Bilateral phacoemulsification with IOL implantation was performed in 6 New Zealand rabbits. Each animal received a study (accommodating) IOL and a control (1-piece hydrophobic acrylic) IOL. Eyes were examined at the slitlamp from 1 day through 6 weeks postoperatively. The globes were then enucleated and evaluated grossly. Capsular bag opacification was scored from the posterior aspect (Miyake-Apple view). The eyes were then processed for complete histopathologic evaluation. RESULTS: At 6 weeks, the mean posterior capsule opacification (PCO) clinical score was 0.5 ± 0.3 (SD) in the study group and 3.0 ± 0.9 in the control group (P=.001, 2-tail paired t test). Anterior capsule opacification was practically absent in the study group and mild in the control group. Miyake-Apple posterior view showed a mean central PCO score of 0 ± 0 in the study group and 3.0 ± 1.1 in the control group (P=.001), peripheral PCO score of 0.7 ± 0.4 and 3.5 ± 0.8 (P=.0006), respectively, and Soemmerring ring score of 2.3 ± 0.8 and 7.0 ± 2.8 (P=.01), respectively. Histopathology showed no signs of toxicity in any eye. CONCLUSIONS: The study IOL maintained an expanded capsular bag secondary to the large size of the haptic elements, which appears to prevent capsular bag opacification.

Pathologic comparison of asymmetric or sulcus fixation of 3-piece intraocular lenses with square versus round anterior optic edges.

OBJECTIVE: To evaluate the pathologic findings of 3-piece intraocular lenses (IOLs) with asymmetric or sulcus fixation in pseudophakic cadaver eyes, comparing IOLs with square or round edges on the anterior optic surface. DESIGN: Comparative case series with pathology. PARTICIPANTS: A total of 661 pseudophakic cadaver eyes, obtained from eye banks within the United States, implanted with different IOLs. METHODS: Anterior segment scanning of whole eyes with a high-frequency ultrasound system or high-resolution anterior segment magnetic resonance imaging followed by gross examination. Selected eyes were processed for complete histopathologic analysis. MAIN OUTCOME MEASURES: Findings from imaging, gross, and histopathologic evaluation that could be related to out-of-the-bag fixation of the lenses. RESULTS: Of 661 pseudophakic cadaver eyes obtained, 13 had 3-piece hydrophobic acrylic IOLs with anterior and posterior square optic edges, and 14 had 3-piece lenses with anterior round edges (13 silicone lenses and 1 hydrophobic acrylic lens) without symmetric in-the-bag fixation. These 27 selected eyes were processed for complete histopathologic analysis. Gross findings in both groups were composed of IOL decentration and tilt, pigmentary dispersion within the anterior segment and on the IOL surface, and iris transillumination defects. Histopathology of the 14 eyes with 3-piece IOLs with round anterior optic edges showed mild focal disruption of the iris pigmented layer and loop protrusion/erosion in the ciliary sulcus. Additional changes observed in the 13 eyes with square anterior optic edge IOLs included iris changes, such as vacuolization, disruption and loss of the pigmented epithelial layers, iris thinning and atrophy, synechiae, and pigmentary dispersion within the trabecular meshwork. One eye also exhibited initial signs of optic nerve disc cupping. CONCLUSIONS: In this series, pathologic findings were more severe in eyes implanted with 3-piece IOLs with square anterior optic edges, suggesting that IOLs with round anterior edges are more suitable for sulcus fixation. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Light scattering and light transmittance in intraocular lenses explanted because of optic opacification.

PURPOSE: To assess light scattering and light transmittance in intraocular lenses (IOLs) explanted because of optic opacification. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. DESIGN: Experimental study. METHODS: Poly(methyl methacrylate) (PMMA) IOLs with snowflake degeneration, hydrophilic acrylic IOLs with different calcification patterns, and 1 calcified silicone IOL explanted from an eye with asteroid hyalosis were studied with gross and light microscopy. Light scattering was measured with an EAS-1000 Scheimpflug camera. Light transmittance was measured with a Lambda 35 UV/Vis spectrophotometer (single-beam configuration with RSA-PE-20 integrating sphere). Analyses were performed at room temperature in the hydrated state and compared with controls. RESULTS: The study evaluated 8 PMMA IOLs, 22 hydrophilic acrylic IOLs, and 1 silicone IOL. Light scattering was as follows: 208 to 223 computer-compatible tapes (CCTs) for PMMA IOLs with snowflake degeneration (control = 9 CCTs); 90 to 227 CCTs for calcified hydrophilic acrylic IOLs (controls = 12 to 23 CCTs); 223 CCTs for the calcified silicone IOL (control = 5 CCTs). The mean light transmittance in the visible light spectrum was 81.08% to 97.10% for PMMA IOLs (control = 98.80%); 78.94% to 97.32% for hydrophilic acrylic IOLs (controls = 97.32% to 98.66%); 94.68% for the silicone IOL (control = 97.74%). CONCLUSION: Intraocular lens opacification led to very high levels of light scattering and a potential for decreased light transmittance, which play a role in the development of symptoms such as glare and halos, decreased contrast sensitivity, and eventually decreased visual acuity. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Prevention of capsular bag opacification with a modified hydrophilic acrylic disk-shaped intraocular lens.

PURPOSE: To evaluate the stability and capsular bag opacification with a modified disk-shaped 1-piece hydrophilic acrylic intraocular lens (IOL) suspended between 2 complete haptic rings connected by a pillar of the haptic material and with a commercially available 1-piece hydrophilic acrylic IOL. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. DESIGN: Experimental study. METHODS: Study and control IOLs were implanted into the left eyes and right eyes of 5 New Zealand rabbits. Eyes were examined at the slitlamp from 1 through 4 weeks. At 4 weeks, the globes were enucleated and evaluated under a very-high-frequency ultrasound. Photographs were taken and capsular bag opacification scored from the posterior aspect (Miyake-Apple view), and the eyes were processed for complete histopathology. RESULTS: At 4 weeks, the posterior capsule opacification score was 0.0 in the study group and 1.75 ± 0.5 (SD) in the control group (P=.005, paired t test). Ultrasound examination showed that 2 of the study IOLs had no contact between the posterior optic surface and the posterior capsule. Minimal proliferative cortical material was confined to the peripheral space between anterior and posterior rings of the study IOL haptics in localized areas at the equatorial region of the capsular bag. Anterior capsule opacification was absent in all eyes. CONCLUSIONS: The study IOL is a modification of a previous design, incorporating haptic perforations between the peripheral rings. By maintaining an open capsular bag and enhancing endocapsular inflow of aqueous, this modified design appears to prevent capsular bag opacification.

Anterior segment optical coherence tomography in the assessment of postoperative intraocular lens optic changes.

PURPOSE: To evaluate the use of anterior segment optical coherence tomography (AS-OCT) to assess postoperative intraocular lens (IOL) optic changes. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. DESIGN: Experimental study. METHODS: Intraocular lenses explanted because of various complications were used, including poly(methyl methacrylate) (PMMA) IOLs with snowflake degeneration, hydrophilic acrylic IOLs with calcification, a silicone IOL with calcification from an eye with asteroid hyalosis, and hydrophobic acrylic IOLs explanted because of decentration, subluxation, or uveitis-glaucoma-hyphema syndrome. After gross and light microscopy, the IOLs were examined in the dry and hydrated states using AS-OCT. Selected hydrophilic acrylic IOLs were stained for calcium. In-the-bag IOLs in pseudophakic cadaver eyes were also evaluated by AS-OCT before and after explantation to confirm correspondence with the clinical situation. RESULTS: Intraoptic changes, such as snowflake lesions in PMMA IOLs, calcification in hydrophilic acrylic IOLs, and glistenings in hydrophobic acrylic IOLs, could be imaged by AS-OCT. The method was also helpful in analyzing the location and density. However, in cases of more superficial changes, unless the lesions/deposits were present on the optic surface with an extension to the optic substance of at least 0.1 mm, they could not be clearly differentiated from the overall outline of the IOL surface. CONCLUSIONS: Anterior segment OCT may be helpful in assessing the presence, location, and density of intraoptic changes, avoiding a misdiagnosis of IOL opacification and the performance of unnecessary procedures, such as posterior capsulotomy or vitrectomy.

Use of loteprednol for routine prophylaxis after photorefractive keratectomy.

BACKGROUND: The purpose of this work is to report our experience using loteprednol 0.5% for routine prophylaxis after photorefractive keratectomy in an academic refractive surgery center. MATERIALS AND METHODS: Photorefractive keratectomy was performed on 579 eyes from 316 patients in this retrospective chart review of patients treated postoperatively with either fluorometholone 0.1% (273 eyes) or loteprednol 0.5% (306 eyes). Primary outcome measures at 6 months included uncorrected distance visual acuity, corrected distance visual acuity, and manifest refraction spherical equivalent. Secondary outcome measures were incidence of corneal haze and increased intraocular pressure. RESULTS: There were no statistically significant differences in preoperative characteristics between the two groups when comparing age, sex, best-corrected visual acuity, spherical equivalent, or keratometry. Both groups achieved excellent visual outcomes, with a mean uncorrected distance visual acuity (logMAR) of 0.004 ± 1.4 in the fluorometholone group and -0.028 ± 1.1 in the loteprednol group (P = 0.013) at 6 months. Postoperative corneal haze and increased intraocular pressure were uncommon and not statistically different between the groups. CONCLUSION: Loteprednol 0.5% performed similarly to fluorometholone 0.1% when used for prophylaxis following photorefractive keratectomy. The incidence of haze and increased intraocular pressure were similar between the two groups.

Long-term pathologic follow-up of obsolete design: Choyce Mark VIII anterior chamber intraocular lens.

We analyzed an enucleated eye that was blind and painful from a 66-year-old patient implanted with a Tennant modification of the Choyce Mark VIII anterior chamber intraocular lens (IOL) as a secondary procedure in 1978. The eye developed glaucoma, with implantation of an Ahmed valve in 2006. Gross and light microscopic analyses showed corneal decompensation and vascularization, peripheral anterior and posterior synechiae, iris thinning, significant changes in the iris pigmented layer, fibrous tissue on the anterior surface of the iris, and Soemmerring ring formation in the periphery of capsular bag remnants. In addition, there was severe attenuation of the nerve fiber layer and extensive cupping of the optic disc. The IOL surface was overall smooth and regular, without warping of the footplates, and was partially covered by clumps of various cell elements, including giant cells intermixed with pigment. This study represents the longest clinicopathologic correlation report on this IOL.