Confocal reflectance microscopy for mapping collagen fiber organization in the vitreous gel of the eye.

Vitreous collagen structure plays an important role in ocular mechanics. However, capturing this structure with existing vitreous imaging methods is hindered by the loss of sample position and orientation, low resolution, or a small field of view. The objective of this study was to evaluate confocal reflectance microscopy as a solution to these limitations. Intrinsic reflectance avoids staining, and optical sectioning eliminates the requirement for thin sectioning, minimizing processing for optimal preservation of the natural structure. We developed a sample preparation and imaging strategy using ex vivo grossly sectioned porcine eyes. Imaging revealed a network of uniform diameter crossing fibers (1.1 ± 0.3 µm for a typical image) with generally poor alignment (alignment coefficient = 0.40 ± 0.21 for a typical image). To test the utility of our approach for detecting differences in fiber spatial distribution, we imaged eyes every 1 mm along an anterior-posterior axis originating at the limbus and quantified the number of fibers in each image. Fiber density was higher anteriorly near the vitreous base, regardless of the imaging plane. These data demonstrate that confocal reflectance microscopy addresses the previously unmet need for a robust, micron-scale technique to map features of collagen networks in situ across the vitreous.

Self-reporting of Conflicts of Interest by Ophthalmology Researchers Compared with the Open Payments Database Industry Reports.

PURPOSE: To evaluate the completeness of conflict-of-interest self-reporting by ophthalmology researchers and to assess factors associated with self-reporting. DESIGN: Cross-sectional observational study. PARTICIPANTS: We evaluated articles published between January and June 2017 in Ophthalmology, JAMA Ophthalmology, the American Journal of Ophthalmology, and Investigative Ophthalmology and Visual Science. To assess more accurately the cases in which an author published multiple articles, we defined a unit of analysis, authorship, for which each author of each article is a unique data point. To enable comparison with the Open Payments Database (OPD), we only included United States physician authorships. METHODS: For each authorship, we defined self-reported relationships as the companies listed in the article's conflict-of-interest disclosures. Based on journal policies, we defined OPD-reported relationships as the list of companies that reported payments to the author within 36 months before submission. MAIN OUTCOME MEASURES: For each authorship, we assessed the proportion of OPD-reported relationships that were self-reported. The primary measurement was the proportion of authorships reporting none of their OPD-reported relationships. RESULTS: Of the 660 total authorships (486 unique authors), 413 authorships (63%) reported none of their OPD-reported relationships, 112 (17%) reported some of them, 9 (1%) reported all of them, and 126 (19%) had 0 relationships. The proportion of authorships reporting none of their relationships did not differ significantly between journals that required reporting of all relationships compared with journals that required reporting only of relevant relationships (adjusted percentage, 61.4% vs. 64.3%; P = 0.46). Authorships with more dollars received during the reporting period showed higher rates of self-reporting (P < 0.001). CONCLUSIONS: Even among journals that required complete reporting, self-reporting was low compared with an industry-maintained database of financial relationships. Deficiencies in reporting may undermine confidence in self-reporting and may compromise the transparency that is needed to interpret research results fairly. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Association between myopia progression and quantity of laser treatment for retinopathy of prematurity.

BACKGROUND: Previous studies found that infants with retinopathy of prematurity (ROP) who were treated for more posterior disease with a greater number of laser spots developed higher myopia. These studies included multiple physicians with variations in laser density. In treatments by a single physician, laser spot count is a better surrogate for area of avascular retina and anterior-posterior location of disease, so that the relationship with myopia can be better assessed. METHODS: Our retrospective study included infants treated with laser for ROP by a single surgeon at a single center. Exclusion criteria were irregularities during laser and additional treatment for ROP. We assessed correlation between laser spot count and change in refractive error over time using a linear mixed effects model. RESULTS: We studied 153 eyes from 78 subjects treated with laser for ROP. The average gestational age at birth was 25.3±1.8 weeks, birth weight 737±248 grams, laser spot count 1793±728, and post-treatment follow up 37±29 months. Between corrected ages 0-1 years, the mean spherical equivalent was +0.4±2.3 diopters; between ages 1-2, it was -1.3±3.2D; and ages 2-3 was -0.8±3.1D. Eyes that received more laser spots had significantly greater change in refractive error over time (0.30D more myopia per year per 1000 spots). None of the eyes with hyperopia before 18 months developed myopia during the follow-up period. CONCLUSIONS: Greater myopia developed over time in infants with ROP treated by laser to a larger area of avascular retina.

Structure and mechanics of the vitreoretinal interface.

Vitreoretinal mechanics plays an important role in retinal trauma and many sight-threatening diseases. In age-related pathologies, such as posterior vitreous detachment and vitreomacular traction, lingering vitreoretinal adhesions can lead to macular holes, epiretinal membranes, retinal tears and detachment. In age-related macular degeneration, vitreoretinal traction has been implicated in the acceleration of the disease due to the stimulation of vascular growth factors. Despite this strong mechanobiological influence on trauma and disease in the eye, fundamental understanding of the mechanics at the vitreoretinal interface is limited. Clarification of adhesion mechanisms and the role of vitreoretinal mechanics in healthy eyes and disease is necessary to develop innovative treatments for these pathologies. In this review, we evaluate the existing literature on the structure and function of the vitreoretinal interface to gain insight into age- and region-dependent mechanisms of vitreoretinal adhesion. We explore the role of vitreoretinal adhesion in ocular pathologies to identify knowledge gaps and future research areas. Finally, we recommend future mechanics-based studies to address the critical needs in the field, increase fundamental understanding of vitreoretinal mechanisms and disease, and inform disease treatments.

PROGRESSION OF PARTIAL POSTERIOR VITREOUS DETACHMENT OVER TIME.

PURPOSE: We investigated interindividual differences in the rate of change of posterior vitreous detachment (PVD) stage and vitreomacular adhesion area (VMAA). Crosssectional studies demonstrated increasing PVD stage and decreasing VMAA with age, but population-level means may mask interindividual variation in the rate of change. METHODS: We retrospectively evaluated PVD stage and VMAA in asymptomatic eyes of subjects who underwent repeated optical coherence tomography screening for high-risk medication use or isolated retinal disease in the fellow eye. A Turnbull estimator modeled changes in the PVD stage, and linear mixed models evaluated VMAA change. RESULTS: We evaluated 101 eyes of 101 subjects. Seventy-six eyes remained in the same stage. Twenty-three eyes progressed to a higher stage. Modeling of longitudinal data predicts that at age 30, time to convert to Stage 4 is 26 years; at age 40, it is 16 years; at age 50, it is 9 years; and at age 60, it is 8 years. In 37 eyes with Stage 1 partial PVD, VMAA decreased at a similar rate. The average population level decline in VMAA was 0.13 mm2/year. CONCLUSION: Individuals vary in age at which they progress to complete PVD. In early partial PVD, VMAA decreases at a similar rate across individuals.

Clinical Outcomes and Lens Constant Optimization of the Zeiss CT Lucia 602 Lens Using a Modified Yamane Technique.

PURPOSE: To report the clinical and refractive outcomes of a modified Yamane technique for scleral fixation of the CT Lucia 602 lens. DESIGN: Retrospective case series. PATIENTS: One hundred twenty-one eyes with dislocated posterior chamber lens implants, surgical aphakia, subluxed crystalline lenses, capsular tear, anterior chamber, or iris sutured posterior chamber lens intolerance were included. METHODS: Secondary implantation of the Zeiss CT Lucia 602 lens was performed by a single surgeon using a modified Yamane technique employing a single needle, rather than the double-needle approach. One hundred twelve eyes underwent simultaneous 3 port pars plana vitrectomy and 9 eyes had previously undergone posterior vitrectomy surgery. Exclusion criteria were age <18, simultaneous glaucoma or corneal procedures, staged corneal transplantation, and follow-up <30 days. MAIN OUTCOME MEASURES: A paired t-test was used to compare pre- and post-operative corrected distance visual acuity (CDVA), the mean predictive error, and the mean absolute predictive error between the manufacturer's and optimized constants for Hoffer Q, Holladay I, and SRK/T. Complication rates were reported. RESULTS: One hundred twenty-one consecutive eyes with a mean follow-up of 237 days were included. The pre-operative CDVA was 0.871 ± 0.785 logMAR (mean ± standard deviation, Snellen equivalent 20/149), which improved to 0.401 ± 0.608 (Snellen equivalent 20/50) post-operatively. In 109 eyes with reliable postoperative refractions, the mean predictive refractive error (D) ± std was +0.74 ± 1.37 for Hoffer Q, +0.66 ± 1.41 for Holladay 1, and +0.47 ± 1.49 for SRK/T (p<0.05). Refractive outcome analysis yielded a mean optimized personalized anterior chamber depth (pACD) of 5.69, Surgeon Factor of 1.79, and A constant of 118.56. Vision-limiting complications occurred in 11 eyes (9.1%). CONCLUSION: Scleral fixation of the CT Lucia 602 lens using a single-needle modification of the Yamane technique resulted in very good visual acuity, predictable postoperative refractive errors, but some vision-limiting complications in this heterogeneous group of eyes with significant comorbidities.

Standard 6-mm Compared with Widefield 16.5-mm OCT for Staging of Posterior Vitreous Detachment.

PURPOSE: To assess whether 6-mm OCT scans, which image the macula, can distinguish complete from partial posterior vitreous detachment (PVD) in comparison with 16.5-mm OCT scans, which image the macula, optic nerve, and mid periphery. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: We compared 6-mm and 16.5-mm scans in 157 eyes of 157 retina clinic patients (mean age, 50 years; range, 10-64 years) with diabetic retinopathy (36%), no retinal disease (19%), and various retinal conditions (45%). We also analyzed 16.5-mm scans in 35 healthy eyes (asymptomatic fellow eyes of patients with unilateral retinal conditions; mean age, 46 years; range, 9-63 years). METHODS: Each participant underwent Heidelberg Spectralis imaging with the standard lens (6-mm scan) and/or the 55° lens (16.5-mm scan). On 6-mm scans, we classified eyes as stage 3 partial PVD when the posterior vitreous cortex was visualized without visible attachment. On 16.5-mm scans, we classified eyes as stage 3 when the vitreous was attached at the optic nerve and separated from the macula. On both scan types, we classified eyes as stage 4 when neither the premacular bursa nor the posterior vitreous cortex were visualized. We assessed the accuracy of this system for detecting complete PVD on 6-mm scans by calculating test characteristics using 16.5-mm scans as a reference standard. MAIN OUTCOME MEASURE: Posterior vitreous detachment stage (0-4). RESULTS: Posterior vitreous detachment stage was identical in 6-mm and 16.5-mm scans in 88% of eyes. Compared with 16.5-mm scans, 6-mm scans detected complete PVD (vs. earlier stages 0-3) with 91% sensitivity and 99% specificity. Seven eyes were classified as no PVD on 6-mm scans and were classified as partial PVD on 16.5-mm scans because vitreoretinal separation was localized to the mid periphery. All 16.5-mm scans showed some degree of PVD, including scans from 9 participants between 9 and 20 years of age. CONCLUSIONS: Six-millimeter scans distinguished complete from partial PVD with good sensitivity and specificity but missed the earliest stages of PVD, which occur in the mid periphery. Posterior vitreous detachment may begin as early as the second decade of life.

Accuracy of Spectral-Domain OCT of the Macula for Detection of Complete Posterior Vitreous Detachment.

PURPOSE: To assess the accuracy of macular spectral-domain OCT in detecting complete posterior vitreous detachment (PVD). DESIGN: Evaluation of diagnostic test or technology using a retrospective comparative study. PARTICIPANTS: One hundred seventy-five eyes in 175 patients (111 women and 64 men; mean age, 65 years) with preoperative OCT within 90 days of vitrectomy. METHODS: Posterior vitreous detachment status on preoperative macular OCT was compared with PVD determination during vitrectomy. Attached vitreous was identified on OCT by visualizing the posterior vitreous cortex or premacular bursa. Complete PVD was identified by the absence of these findings and considered a positive outcome for the purpose of analysis. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive predictive value, and negative predictive value of macular OCT for detection of complete PVD compared with findings at surgery. RESULTS: Of the 38 eyes graded as showing complete PVD on OCT, 20 eyes were found to have pre-existing PVD at the time of surgery (true-positive results), and 18 eyes were found to have attached vitreous at the time of surgery (false-positive results). Of the 137 eyes graded as showing attached vitreous on OCT, 129 eyes had attached vitreous at the time of surgery (true-negative results), and 8 eyes had pre-existing PVD at the time of surgery (false-negative results). The sensitivity of OCT for detecting complete PVD was 71% and the specificity was 88%. In the study population, the positive predictive value of an OCT scan showing complete PVD was 53%, whereas the negative predictive value of an OCT scan showing attached vitreous was 94%. CONCLUSIONS: If the premacular bursa or posterior vitreous cortex are visualized on macular OCT, an accurate determination of attached vitreous can be made. The diagnosis of complete PVD by macular OCT is less accurate and requires ultrasound.

Progressive optic nerve changes in cavitary optic disc anomaly: integration of copy number alteration and cis-expression quantitative trait loci to assess disease etiology.

BACKGROUND: We performed clinical and genetic characterization of a family with cavitary optic disc anomaly (CODA), an autosomal dominant condition that causes vision loss due to adult-onset maculopathy in the majority of cases. CODA is characterized by a variably excavated optic nerve appearance such as morning glory, optic pit, atypical coloboma, and severe optic nerve cupping. METHODS: Four affected and fourteen unaffected family members of a multi-generation pedigree were phenotyped by visual acuity, intraocular pressure, dilated fundus examination, fundus photography, and optical coherence tomography. Genetic analysis was performed by breakpoint polymerase chain reaction (PCR), long range PCR, and direct Sanger sequencing. The functional relevance of the copy number alteration region was assessed by in silico analysis. RESULTS: We found progressive optic nerve cupping in three affected members of a family with CODA. In one individual, an optic pit developed over time from a normal optic nerve. By two independent methods, we detected a previously described intergenic triplication that segregated with disease in all adults of the family. The copy number alteration was also detected in five children with normal optic nerves. eQTL analysis demonstrated that this CNA region regulates expression of up to 4 genes in cis. CONCLUSIONS: Morning glory, optic pit and atypical coloboma are currently considered congenital anomalies of the optic nerve, but our data indicate that in CODA, the excavated optic nerve appearance may develop after birth and into adulthood. In silico analysis of the CNA, may explain why vairable expressivity is observed in CODA.

Removal of calcific band keratopathy without ethylenediaminetetraacetic acid (EDTA) in eyes with limited visual potential.

PURPOSE: Treatment of calcific band keratopathy (CBK) is commonly performed with ethylenediaminetetraacetic acid (EDTA), but EDTA has become more difficult to obtain. This paper describes a technique for treating CBK using a diamond-dusted burr without EDTA in eyes with limited visual potential. PATIENTS AND METHODS: In this paper, we provide detailed instructions on how to perform the surgical technique for treating CBK, along with a surgical video. We performed a retrospective review of consecutive patients with clinically significant CBK who underwent this procedure from December 2012 to July 2015. RESULTS: Seven eyes of six patients were included for analysis. Preoperatively, all patients suffered from ocular discomfort. All eyes had poor preoperative visual acuity due to non-corneal ocular disease. The most common causes of CBK in this series were retinopathy of prematurity (three eyes) and chronic uveitis (two eyes). Postoperatively, all patients reported partial or complete relief of discomfort. The length of follow-up ranged from 15 days to 31 months. Two eyes experienced recurrence of CBK. This occurred at 4 and 28 months after treatment. CONCLUSION: The diamond-dusted burr can easily and effectively remove the corneal epithelium and underlying calcium deposits. Therefore, it may be used to effectively treat discomfort from CBK.

Stroke Due to Cerebral Vasculitis in a Patient with Relentless Placoid Chorioretinitis.

PURPOSE: To report the first case of stroke in a patient with relentless placoid chorioretinitis. METHODS: Observational case report. RESULTS: A 20-year-old female with newly diagnosed relentless placoid chorioretinitis was urgently evaluated for unilateral paresthesias. She was found to have acute bilateral pontine strokes and cerebral vasculitis on magnetic resonance imaging of the brain and cerebral angiography. CONCLUSIONS: We report the first case of stroke due to cerebral vasculitis in a patient with relentless placoid chorioretinitis. This case emphasizes the need for timely evaluation of neurological symptoms in patients with this ocular diagnosis.

Corneal biomechanical properties after laser-assisted in situ keratomileusis and photorefractive keratectomy.

BACKGROUND: The purpose of this study was to evaluate the effects of laser-assisted in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) on corneal biomechanical properties. METHODS: We used the ocular response analyzer to measure corneal hysteresis (CH) and corneal resistance factor (CRF) before and after refractive surgery. RESULTS: In all, 230 eyes underwent LASIK and 115 eyes underwent PRK without mitomycin C (MMC). Both procedures decreased CH and CRF from baseline. When MMC was used after PRK in 20 eyes, it resulted in lower corneal biomechanical properties at 3 months when compared to the other procedures, but all three procedures had similar values at 12 months. CONCLUSION: Significant but similar decreases in corneal biomechanical properties after LASIK, PRK without MMC, and PRK with MMC were noted.

Levetiracetam: an unusual cause of delirium.

Levetiracetam is a second-generation anticonvulsant that was approved by the Federal Drug Administration in 1999 for the treatment of epilepsy. Recently, levetiracetam has become more popular for the prevention of posttraumatic seizures. Some of the well-known adverse effects of levetiracetam are somnolence, behavioral abnormalities, and less commonly, psychosis. Delirium is not a well-known adverse effect of levetiracetam. Here, we present the case of a 77-year-old Caucasian male who developed disorientation, agitation, and lethargy after initiation of levetiracetam to prevent posttraumatic seizures. Imaging on admission demonstrated a subacute subdural hematoma in the left frontal lobe without mass effect, and the patient was started on levetiracetam 500 mg intravenously twice daily. Less than 24 hours later, the patient began to display a fluctuating level of consciousness, disorientation, an inability to follow commands, and garbled speech. His symptoms continued for 12 days unabated despite episodic treatment with sedatives and antipsychotics. At one point, the patient progressed to aggressive behavior and required restraints. Laboratory tests during this period did not demonstrate signs of infection or metabolic abnormalities. Delirium from levetiracetam was suspected and the drug was discontinued. The patient's mental status improved dramatically within 24 hours after administration of the last dose of levetiracetam and he was discharged home. Based on the Naranjo scale, the episode of delirium was probably related to levetiracetam. Although the other neuropsychiatric effects of levetiracetam are well known, we highlight the first case of delirium without psychotic features associated with levetiracetam.