Asteroid Hyalosis: An Update on Prevalence, Risk Factors, Emerging Clinical Impact and Management Strategies.

Asteroid hyalosis (AH) is a benign clinical entity characterized by the presence of multiple refractile spherical calcium and phospholipids within the vitreous body. First described by Benson in 1894, this entity has been well documented in the clinical literature and is named due to the resemblance of asteroid bodies on clinical examination to a starry night sky. Today, a growing body of epidemiologic data estimates the global prevalence of asteroid hyalosis to be around 1%, and there is a strong established association between AH and older age. While pathophysiology remains unclear, a variety of systemic and ocular risk factors for AH have recently been suggested in the literature and may provide insight into possible mechanisms for asteroid body (AB) development. As vision is rarely affected, clinical management is focused on differentiation of asteroid hyalosis from mimicking conditions, evaluation of the underlying retina for other pathology and consideration of vitrectomy in rare cases with visual impairment. Taking into account the recent technologic advances in large-scale medical databases, improving imaging modalities, and the popularity of telemedicine, this review summarizes the growing body of literature of AH epidemiology and pathophysiology and provides updates on the clinical diagnosis and management of AH.

Effect of surgical modality on visual outcomes for young patients with primary rhegmatogenous retinal detachments: a retrospective cohort study.

OBJECTIVE: To examine outcomes of different surgical modalities for correcting primary rhegmatogenous retinal detachments in patients younger than 50 years of age. METHODS AND ANALYSIS: A single-centre, retrospective, cohort study of 754 patients who underwent retinal surgery at the University of Virginia Hospital between 1 July 2012 and 1 July 2020 was conducted. Exclusion criteria were patients less than 18 or over 50 years of age, repeat detachments, second eyes of patients with bilateral detachments and follow-up less than 3 months. A multivariate regression model was used to compare overall outcomes in patients. RESULTS: 86 patients met inclusion criteria and of those, 38 (44%) underwent vitrectomy, 22 (26%) underwent scleral buckling, 13 (15%) underwent pneumatic retinopexy and 13 (15%) underwent combined scleral buckle and vitrectomy repair. Comparison of eye-level parameters among the procedure groups shows difference with respect to macular involvement (p<0.05) but not regarding clock hour involvement or giant tear status (p>0.05). Preoperative visual acuity was superior in the scleral buckle group compared with vitrectomy (p<0.001). Mean postoperative visual acuity improved with all procedures and all repair procedures had comparable rates of complication. The mean overall anatomical success rate was 73% (n=63) and comparable among all modalities. CONCLUSIONS: Vitrectomy, scleral buckle, pneumatic retinopexy or combined procedures are viable repair options for rhegmatogenous retinal detachments in patients younger than 50 years of age. Selection of the repair modality should be guided on baseline clinical features of the patient and detachment.

Effect of surgical timing in 23-g pars plana vitrectomy for primary repair of macula-off rhegmatogenous retinal detachment, a retrospective study.

BACKGROUND: Rhegmatogenous retinal detachment (RRD) is a common, potentially blinding ocular pathology that is considered a surgical emergency. Macular involvement has been identified as a major negative prognostic indicator for visual recovery after RRD correction. It is not currently clear whether early intervention improves visual outcomes, and in practice, there are potential disadvantages to performing early surgery for fovea-involving RRD. Such disadvantages include inadequate assessment of coexisting comorbidities, increased rate of complications related to poorly trained staff or tired surgeons, and anesthetic risk. METHODS: A single-center, retrospective, cohort study of patients who underwent repair of macula-involving rhegmatogenous retinal detachment at the University of Virginia was performed. Variables collected included patient demographics, ocular history, clinical characteristics, and post-operative complications. Patients were excluded if they had a history of congenital or acquired pathology with an effect on visual function, bilateral or repeat rhegmatogenous detachment, age less than 18 years, follow up duration less than 6 months, or if they were repaired using scleral buckle, pneumatic retinopexy, 25- or 27-gauge pars plana vitrectomy, or any combination of these techniques. A multivariate regression model was used to compare overall outcomes such as post-operative visual acuity, intra-ocular pressure, retina attachment status, and complications among patients of differing timing of surgical repair. These analyses were adjusted for clinical factors known or considered to be associated with worse prognosis in rhegmatogenous retinal detachment. RESULTS: A total of 104 patients undergoing 23-gauge vitrectomy for repair of macula involving rhegmatogenous retinal detachments were included in this study with mean follow up period 17.9 ± 14.1 months. Early surgical repair (< 48 h) was pursued in 26 patients, moderately delayed surgical repair (3-7 days), was performed in 29 patients and late surgical repair (> 7 days) in 49 patients. Our analysis showed no difference in post-operative visual acuity between patients with detachments undergoing early versus moderately delayed repair of RRD. However, mean visual acuity differed between patients undergoing early versus late repair at 3, 6, and 12 months. No significant difference was observed in post-operative complications between the three surgical timepoints including cataract formation, development of glaucoma and re-detachment rate. Use of 360 laser was found to be protective against re-detachment overall (OR 6.70 95% CI 1.93-23.2). CONCLUSIONS: These findings indicate that a moderate delay of 3-7 days from symptom onset for repair of macula-involving retinal detachment may be a safe approach as there are no differences in terms of visual acuity or post-operative complications compared to early repair within 48 h. Delaying surgery for > 7 days however is not recommended due to the loss of recovery of visual acuity observed in this study. Use of 360 laser may prevent risk of re-detachment after primary repair.

Tissue Plasminogen Activator Effects on Fibrin Volume and the Ocular Proteome in a Juvenile Rabbit Model of Lensectomy.

Purpose: To investigate the use of tissue plasminogen activator (tPA) and its effects on the ocular proteome as a therapeutic intervention for postoperative inflammation and fibrin formation following intraocular lens (IOL) insertion in a juvenile rabbit model. Methods: Twenty-six rabbits, 6 to 7 weeks old, underwent lensectomy with IOL insertion. Following examination on day 3, 100 µL of either 25 µg of recombinant rabbit tPA or balanced salt solution (control) was injected into the anterior chamber. On postoperative day 4, rabbits underwent examination, and eyes were harvested and fixed for 9.4-Tesla magnetic resonance imaging (MRI). Three masked observers quantified fibrin scar volume using Horos Project software. Aqueous humor (AH) was collected immediately prior to surgery and on postoperative days 3 and 4. Proteins related to coagulation and inflammation were assessed in AH samples using targeted mass spectrometry via parallel reaction monitoring. Results: tPA significantly reduced the volume of fibrin 24 hours following administration compared with control eyes (0.560 mm3 vs. 3.29 mm3; P < 0.0001). Despite the reduced fibrin scar, proteins related to the coagulation and complement cascade were not significantly different following tPA injection. Conclusions: tPA may be a safe candidate for reduction of postoperative fibrin scarring after intraocular surgery. MRI can provide a quantitative value for fibrin volume changes. Translational Relevance: tPA is a candidate to treat ocular fibrin scarring. MRI can quantify the efficacy of treatments in future dose-response studies. Targeted mass spectrometry can provide critical data necessary to help decipher the effect on the abundance of targeted proteins following pharmacological intervention.

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.

Use of a Juvenile Rabbit Animal Model to Evaluate Therapeutic Interventions for Postoperative Inflammation and Fibrin Formation After Lensectomy.

PURPOSE: We used the juvenile rabbit as a model for investigating therapeutic interventions for postoperative inflammation and fibrin formation following intraocular lens (IOL) insertion for management of pediatric cataracts. METHODS: Twelve 6- to 7-week-old, 600 to 900 g rabbits underwent bilateral clear-cornea lensectomy via irrigation and aspiration with IOL insertion. Following wound closure, enoxaparin 8 mg (n = 6 eyes), preservative-free triamcinolone 0.5 mg (n = 6), 8 mg enoxaparin plus 0.5 mg triamcinolone (n = 6), or balanced salt solution (n = 6) was injected into the anterior chamber. Slit-lamp examinations and optical coherence tomography (OCT) scans were performed postoperatively on days 3 through 7, and 14 to characterize levels of inflammation and fibrin. Using 17 additional rabbits, enzyme-linked immunosorbent assays (ELISAs) with 100 µL of aqueous humor were performed to quantify the amount of fibrinogen and fibrin preoperatively and on postoperative day 3. Immunohistochemistry was performed to confirm the presence of fibrin. RESULTS: Enoxaparin alone and combined with triamcinolone reduced the amount of fibrin present in the anterior chamber compared to untreated eyes, which corresponded to an increase in OCT signal strength. Despite the clear visual axis shown in clinical images, the combination treatment group had the highest levels of soluble fibrin when assessed by ELISA. Immunohistochemistry confirmed the presence of insoluble fibrin seen clinically. CONCLUSIONS: A combination of enoxaparin and triamcinolone appears to provide the most therapeutic benefit by reducing fibrin formation and postoperative inflammation. TRANSLATIONAL RELEVANCE: The juvenile rabbit is an excellent model to investigate inflammation and fibrin formation following lensectomy with IOL insertion and possibly any intraocular surgery in children.

Cytochrome P450 2C epoxygenases mediate photochemical stress-induced death of photoreceptors.

Degenerative loss of photoreceptors occurs in inherited and age-related retinal degenerative diseases. A chemical screen facilitates development of new testing routes for neuroprotection and mechanistic investigation. Herein, we conducted a mouse-derived photoreceptor (661W cell)-based high throughput screen of the Food and Drug Administration-approved Prestwick drug library to identify putative cytoprotective compounds against light-induced, synthetic visual chromophore-precipitated cell death. Different classes of hit compounds were identified, some of which target known genes or pathways pathologically associated with retinitis pigmentosa. Sulfaphenazole (SFZ), a selective inhibitor of human cytochrome P450 (CYP) 2C9 isozyme, was identified as a novel and leading cytoprotective compound. Expression of CYP2C proteins was induced by light. Gene-targeted knockdown of CYP2C55, the homologous gene of CYP2C9, demonstrated viability rescue to light-induced cell death, whereas stable expression of functional CYP2C9-GFP fusion protein further exacerbated light-induced cell death. Mechanistically, SFZ inhibited light-induced necrosis and mitochondrial stress-initiated apoptosis. Light elicited calcium influx, which was mitigated by SFZ. Light provoked the release of arachidonic acid from membrane phospholipids and production of non-epoxyeicosatrienoic acid metabolites. Administration of SFZ further stimulated the production of non-epoxyeicosatrienoic acid metabolites, suggesting a metabolic shift of arachidonic acid under inhibition of the CYP2C pathway. Together, our findings indicate that CYP2C genes play a direct causative role in photochemical stress-induced death of photoreceptors and suggest that the CYP monooxygenase system is a risk factor for retinal photodamage, especially in individuals with Stargardt disease and age-related macular degeneration that deposit condensation products of retinoids.

Genetic variation is the major determinant of individual differences in leukocyte endothelial adhesion.

OBJECTIVE: To determine the genetic contribution to leukocyte endothelial adhesion. METHODS: Leukocyte endothelial adhesion was assessed through a novel cell-based assay using human lymphoblastoid cell lines. A high-throughput screening method was developed to evaluate the inter-individual variability in leukocyte endothelial adhesion using lymphoblastoid cell lines derived from different donors. To assess heritability, ninety-two lymphoblastoid cell lines derived from twenty-three monozygotic twin pairs and twenty-three sibling pairs were compared. These lymphoblastoid cell lines were plated with the endothelial cell line EA.hy926 and labeled with Calcein AM dye. Fluorescence was assessed to determine endothelial cell adhesion to each lymphoblastoid cell line. Intra-pair similarity was determined for monozygotic twins and siblings using Pearson pairwise correlation coefficients. RESULTS: A leukocyte endothelial adhesion assay for lymphoblastoid cell lines was developed and optimized (CV = 8.68, Z'-factor = 0.67, SNR = 18.41). A higher adhesion correlation was found between the twins than that between the siblings. Intra-pair similarity for leukocyte endothelial adhesion in monozygotic twins was 0.60 compared to 0.25 in the siblings. The extent to which these differences are attributable to underlying genetic factors was quantified and the heritability of leukocyte endothelial adhesion was calculated to be 69.66% (p-value<0.0001). CONCLUSIONS: There is a heritable component to leukocyte endothelial adhesion. Underlying genetic predisposition plays a significant role in inter-individual variability of leukocyte endothelial adhesion.