Bilateral Combined Rhegmatogenous and Tractional Retinal Detachments Due to Persistent High-Titer Syphilis.

A 23-year-old man developed bilateral rhegmatogenous retinal detachments secondary to high-titer ocular syphilis. The patient's titer increased four-fold after completing a 14-day course of intravenous penicillin (IVP). He underwent bilateral pars plana vitrectomy with silicone oil fill in both eyes. In this article, the authors propose an updated treatment method for patients with advanced ocular syphilis that includes oral doxycycline for 30 days following 14 days of IVP to optimally minimize the patient's infectious burden. Following surgery and this new treatment regime, this patient's best-corrected visual acuity 10 weeks postoperatively measured 20/50 in the right eye and 20/30 in the left eye. This case highlights a rare but devastating complication of ocular syphilis. We suggest the addition of oral doxycycline to IVP for patients with syphilis titers ≥ 1:256, HIV co-infection, and presence of posterior retinitis. [Ophthalmic Surg Lasers Imaging Retina 2024;55:46-50.].

Proliferative Diabetic Retinopathy Requiring Vitrectomy Over Clinic Management During COVID-19: Impact of Delayed Care.

PURPOSE: This study aimed to investigate the impact of delayed retinal clinical care during the COVID-19 pandemic on the severity of proliferative diabetic retinopathy (PDR) and drivers of follow-up delay. We compared disease severity and follow-up rates of PDR patients requiring vitrectomy to those managed nonsurgically, and identified factors associated with need for vitrectomy. METHODS: The study included 739 patients diagnosed with PDR between January 1, 2018, and March 4, 2021, categorized into two groups based on outcome: vitrectomy nonvitrectomy. Statistical methods such as t-tests and chi-square tests were used to analyze differences in disease severity and follow-up rates before and after COVID-19 shutdown. A multivariate regression evaluated factors leading to vitrectomy by comparing initial ETDRS (Early Treatment of Diabetic Retinopathy Study) DR staging, disease stability, DR progression, proliferative complications, appointment intervals, follow-up variance, rescheduling rate, and no-show rate. RESULTS: Of the 739 patients, 202 required vitrectomy, 537 were managed nonsurgically. The vitrectomy group had more severe or unstable disease before shutdown. The interval between patient visits preshutdown was 29.76 ± 45.11 days in the vitrectomy group and 40.23 ± 56.73 days in the nonvitrectomy group (p < 0.001). Both groups experienced a significant increase in appointment intervals after shutdown, with the vitrectomy group having a greater increase. Both groups had significantly increased rescheduling rate and minimally increased no-show rate. Patient-directed rescheduling was the main driver of appointment delays. Disease factors, such as tractional retinal detachment and higher ETDRS DR staging, increased the odds of vitrectomy, while appointment burden and follow-up variability had a minimal impact. CONCLUSIONS: Patients with more severe PDR and greater delay in appointments due to the pandemic were more likely to require vitrectomy for proliferative complications. Patient-directed rescheduling was identified as the main driver of care delays, as opposed to clinic-directed rescheduling. This study highlights the importance of maintaining regular follow-up appointments for PDR patients during pandemics.

Visual outcomes of acute bacterial endophthalmitis treated with adjuvant intravitreal dexamethasone: A meta-analysis and systematic review.

Adjunctive treatment of bacterial endophthalmitis with intravitreal steroids is a topic of controversy among many ophthalmologists. The objective of this study is to evaluate the effects of intravitreal dexamethasone on the visual outcomes of patients with acute bacterial endophthalmitis through a systematic review and meta-analysis. A literature search of PubMed, Scopus, and Cochrane Library databases was performed to include studies on the visual outcomes of adjuvant intravitreal dexamethasone in patients with acute bacterial endophthalmitis. The review is based on the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) protocol. A total of 1545 articles met our search criteria and after further review, two randomized controlled trials and three retrospective case series were included in the final analysis. A total of 126 eyes were treated with intravitreal dexamethasone combined with antibiotics, and another 139 eyes were treated with antibiotics alone. All cases of endophthalmitis were post-operative or post-intravitreal injection, with pooled results demonstrating no visual benefit with supplementation of intravitreal dexamethasone. Our meta-analysis does not show any visual benefit from steroid supplementation and yet, considering a relatively small number of patients included in each study, larger randomized controlled trials are required to further clarify the role of steroids in the treatment of acute bacterial endophthalmitis.

The Effects of Hyperbaric Oxygen Therapy in Patients with Central Retinal Artery Occlusion: A Retrospective Study, Systematic Review, and Meta-analysis.

PURPOSE: Central retinal artery occlusion (CRAO) is a vision-threatening condition with a potentially poor visual prognosis. Many different treatment modalities are suggested but controversy remains regarding effectiveness of these treatments. The purpose of this study is to perform a systematic review and meta-analysis in addition to analyzing retrospective data at our own tertiary care center regarding effectiveness of hyperbaric oxygen therapy (HBOT) in treatment of CRAO. METHODS: The PubMed, Scopus, and the Cochrane Library are searched from the date of database inception to September 2021 to conduct a review based on the PRISMA (preferred reporting items for systematic review and meta-analysis), evaluating the role of HBOT in visual recovery of CRAO patients. In addition, a retrospective chart review of patients clinically diagnosed with CRAO at our university-based hospital (University of Texas Health, San Antonio, TX, USA) from year 2011 to 2021 was conducted. RESULTS: After a review of 376 articles, three articles met the inclusion criteria for meta-analysis, where a total of 207 patients received HBOT versus 89 patients that did not receive any form of oxygen therapy. Analysis of these results demonstrate that HBOT in CRAO patients does not enhance the final visual outcome (p = 0.83). Similar conclusion was also drawn from retrospective analysis of 48 patients (15 HBOT versus 33 controls) at our tertiary care center, where no visual benefit was observed in the HBOT group. CONCLUSIONS: HBOT does not appear to improve final visual outcome and concerns remain regarding adverse reactions such as barotrauma and generalized seizures. Large, randomized studies are required for further understanding of the role of HBOT in treatment of CRAO.

Diabetic mice have retinal and choroidal blood flow deficits and electroretinogram deficits with impaired responses to hypercapnia.

PURPOSE: The purpose of this study was to investigate neuronal and vascular functional deficits in the retina and their association in a diabetic mouse model. We measured electroretinography (ERG) responses and choroidal and retinal blood flow (ChBF, RBF) with magnetic resonance imaging (MRI) in healthy and diabetic mice under basal conditions and under hypercapnic challenge. METHODS: Ins2Akita diabetic (Diab, n = 8) and age-matched, wild-type C57BL/6J mice (Ctrl, n = 8) were studied under room air and moderate hypercapnia (5% CO2). Dark-adapted ERG a-wave, b-wave, and oscillatory potentials (OPs) were measured for a series of flashes. Regional ChBF and RBF under air and hypercapnia were measured using MRI in the same mice. RESULTS: Under room air, Diab mice had compromised ERG b-wave and OPs (e.g., b-wave amplitude was 422.2±10.7 µV in Diab vs. 600.1±13.9 µV in Ctrl, p < 0.001). Under hypercapnia, OPs and b-wave amplitudes were significantly reduced in Diab (OPs by 30.3±3.0% in Diab vs. -3.0±3.6% in Ctrl, b-wave by 17.9±1.4% in Diab vs. 1.3±0.5% in Ctrl). Both ChBF and RBF had significant differences in regional blood flow, with Diab mice having substantially lower blood flow in the nasal region (ChBF was 5.4±1.0 ml/g/min in Diab vs. 8.6±1.0 ml/g/min in Ctrl, RBF was 0.91±0.10 ml/g/min in Diab vs. 1.52±0.24 ml/g/min in Ctrl). Under hypercapnia, ChBF increased in both Ctrl and Diab without significant group difference (31±7% in Diab vs. 17±7% in Ctrl, p > 0.05), but an increase in RBF was not detected for either group. CONCLUSIONS: Inner retinal neuronal function and both retinal and choroidal blood flow were impaired in Diab mice. Hypercapnia further compromised inner retinal neuronal function in diabetes, while the blood flow response was not affected, suggesting that the diabetic retina has difficulty adapting to metabolic challenges due to factors other than impaired blood flow regulation.

Unusual presentation of CREST retinal vasculitis.

PURPOSE: To report a case of CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias) syndrome-induced retinal vasculitis in the setting of ocular inflammation soon after recent micropulse cyclophotocoagulation (mTS-CPC). OBSERVATIONS: Our patient developed CREST associated retinal vasculitis in both eyes (right > left) eight days after receiving mTS-CPC in her left eye. There was initial concern for sympathetic ophthalmia due to the resulting bilateral inflammation. The patient was treated with prednisone with resolution of her symptoms. CONCLUSIONS: This is the first case of CREST retinal vasculitis that appears to be directly triggered by inflammation caused by mTS-CPC.

Protective Role of 360° Laser Retinopexy in Patients with Rhegmatogenous Retinal Detachment: a Systematic Review and Meta-analysis.

PURPOSE: Visual impairment from retinal re-detachment could be debilitating. The aim of this review is to evaluate the role of 360° laser retinopexy on success rate of rhegmatogenous retinal detachment (RRD) repair by a meta-analysis study. METHODS: The PubMed, Scopus, and the Cochrane Library databases were searched comprehensively from the date of database inception to January 2021, evaluating the role of 360° laser retinopexy in visual and anatomical success rate of RRD repair. This review was conducted based on the preferred reporting items for systematic review and meta-analysis (PRISMA) protocols. RESULTS: Among 202 articles screened for eligibility, six studies were found to be eligible for inclusion in our final analysis. Our meta-analysis demonstrates that prophylactic treatment with circumferential laser photocoagulation has no significant effect on the initial rate of retinal re-detachment or final best-corrected visual acuity following pars plana vitrectomy repair of RRD. Subgroup analysis of studies (n = 3) with 23-gauge pars plana vitrectomy, however, favors attachment rate in patients undergoing 360° prophylactic laser treatment. CONCLUSIONS: Three hundred and sixty degree laser retinopexy appears to have favorable outcomes in patients undergoing 23-gauge retinal detachment repair. This protective effect, however, is not apparent with inclusion of 20-gauge vitrectomy studies.

Treatment of central serous chorioretinopathy with topical NSAIDs.

PURPOSE: Central serous chorioretinopathy (CSCR) is a common retinopathy that is often observed until resolution. The purpose of this study is to evaluate the effects of topical nonsteroidal anti-inflammatory drugs (NSAIDs) on timing of CSCR recovery. METHODS: An IRB-approved retrospective review was conducted on patients that had been diagnosed with a new-onset, symptomatic case of CSCR. Patients were either observed only (13 untreated eyes) or treated with topical bromfenac or nepafenac (14 eyes) over an average of about a 4-5 week follow-up period. RESULTS: There was no statistical significance between central macular thickness (CMT) and visual acuity of treatment and control groups at the initial presentation. However, at the follow-up visit, CMT reductions in the treatment group were significantly higher than in the control group (p<0.006). CONCLUSION: Use of topical NSAIDs in the treatment of acute CSCR leads to a faster rate of reduction in the subretinal fluid volume over a follow-up period of a few weeks.

The effects of temporary intraocular pressure spikes after intravitreal dexamethasone implantation on the retinal nerve fiber layer.

Background and objective: The dexamethasone (DEX) implant is known to cause temporary intraocular pressure (IOP) spikes after implantation. The purpose of this study is to determine if IOP spikes after DEX implant cause significant thinning in the retinal nerve fiber layer (RNFL). Study design, patients, and methods: A total of 306 charts were reviewed with 48 and 21 patients meeting inclusion criteria for the cross-sectional and prospective groups, respectively. Cross-sectional inclusion criteria: IOP spike ≥22 mmHg up to 16 weeks after DEX implant, DEX implant in only 1 eye per patient, and spectral-domain optical coherence tomography (OCT) RNFL imaging of both eyes ≥3 months after IOP spike. Prospective inclusion criteria: OCT RNFL performed within 1 year prior to DEX implantation, IOP spike ≥22 mmHg up to 16 weeks after DEX implant, and OCT RNFL performed ≥3 months after IOP spike. The average RNFL thickness in the contralateral eye was used as the control in the cross-sectional group. Institutional review board approval was obtained. Results: In the cross-sectional group, there was no statistically significant difference in the mean RNFL thicknesses in the treated vs untreated eyes (80.4±15.5 µm and 82.6±15.8 µm, respectively; P=0.33) regardless of treatment diagnosis, magnitude of IOP spike, or history of glaucoma. In the prospective group, mean RNFL thicknesses before and after IOP spikes ≥22 mmHg were similar (78.0±14.8 µm and 75.6±13.6 µm, respectively; P=0.13). Conclusion and relevance: Temporary elevation of IOP after DEX implantation when treated with topical IOP lowering drops does not appear to lead to a meaningful change in RNFL thickness.

The effects of repeated Ozurdex injections on ocular hypertension.

PURPOSE: The purpose of this study was to correlate the degree of ocular hypertension with the number of Ozurdex injections. METHODS: Intraocular pressure (IOP) fluctuations for a total of 183 injections were studied over a period of at least 12 months. The main indications for treatment were uveitis, diabetic macular edema, and retinal vein occlusion. RESULTS: Results of the study demonstrate that repeated Ozurdex injections do not increase the frequency of IOP spikes beyond 30 mmHg. For lower IOPs, however, a positive correlation exists. Furthermore, patients with primary open angle glaucoma and uveitis had the highest IOP response to repeated injections. On average, patients with an IOP of ≥28.6 mmHg received pressure lowering medications, after which their IOP reached a stable level (16.7 mmHg) without the need for additional interventions. CONCLUSION: The data support the conclusion that multiple Ozurdex injections does not increase the frequency of IOP spikes beyond 30 mmHg, but patients still must be closely monitored if they have a history of primary open angle glaucoma.

Resolution of macular edema in radiation retinopathy after intravenous diuresis.

PURPOSE: To report resolution of bilateral macular edema secondary to radiation retinopathy after intravenous diuresis. METHODS: Observational case report, consisting of clinical examination, fluorescein angiography, and optical coherence tomography. RESULTS: A 38-year-old woman developed radiation retinopathy and severe macular edema secondary to whole brain radiation therapy for metastatic breast cancer. After diuresis with intravenous furosemide for pleural effusion, the bilateral macular edema resolved. CONCLUSION: In select patients, systemic diuresis may aid in resolving macular edema.

Complement, innate immunity and ocular disease.

The complement system is a major component of innate immunity. During an inflammatory reaction, the eye is potentially threatened by homologous complement attack, and unregulated complement activation could lead to tissue damage and vision loss. The complement system is continuously activated at low levels in the normal eye, and intraocular complement-regulatory proteins (CRPs) tightly regulate this spontaneous complement activation so that there is elimination of potential pathogens without the induction of destructive intraocular inflammation. The presence of a complement activation product (iC3b) during the early phase of antigen and antigen-presenting cell contact is essential for the induction of systemic tolerance to antigen injected into the anterior chamber of the eye and the establishment of ocular immune privilege. The complement system and complement-regulatory proteins control intraocular inflammation in autoimmune anterior uveitis and may play an important role in the development of age-related macular degeneration. Thus, in the eye, complement functions as a double-edged sword - on one hand it provides innate immunity against pathogens while simultaneously instructing the adaptive immune response to develop tolerance to such pathogens to avoid inadvertent tissue damage in a critical organ.

Complement activation via alternative pathway is critical in the development of laser-induced choroidal neovascularization: role of factor B and factor H.

The objective of this study was to explore the role of classical, lectin, and alternative pathways of complement activation in laser-induced choroidal neovascularization (CNV). The classical and alternative pathways were blocked in C57BL/6 mice by small interfering RNAs (siRNA) directed against C1q and factor B, respectively. C4(-/-) mice developed CNV similar to their wild-type controls and inhibition of C1q by siRNA had no effect on the development of CNV. In contrast, CNV was significantly inhibited (p < 0.001) in C5(-/-) mice and C57BL/6 mice treated with factor B siRNA. Inhibition of the alternative pathway by factor B siRNA resulted in decreased levels of membrane attack complex and angiogenic factors-vascular endothelial growth factor and TGF-beta2. Furthermore, factor B was up-regulated in complement sufficient C57BL/6 mice at day 1 postlaser and remained elevated at day 7. Significantly reduced levels of factor H were observed at day 3 in these animals. In conclusion, our results demonstrate that activation of the factor B-dependent alternative pathway, but not the classical or lectin pathways, was essential for the development of CNV in mouse model of laser-induced CNV. Thus, specific blockade of the alternative pathway may represent a therapeutically relevant strategy for the inhibition of CNV.

Suppression of complement regulatory proteins (CRPs) exacerbates experimental autoimmune anterior uveitis (EAAU).

This study was undertaken to explore the role of complement regulatory proteins (CRPs) in experimental autoimmune anterior uveitis (EAAU). We observed that the levels of CRPs, Crry and CD59, in the eyes of Lewis rats increased during EAAU and remained elevated when the disease resolved. The in vivo role of these CRPs in EAAU was explored using neutralizing mAbs, antisense oligodeoxynucleotides (AS-ODNs), and small interfering RNAs against rat Crry and CD59. Suppression of Crry in vivo at days 9, 14, or 19 by neutralizing mAb or AS-ODNs resulted in the early onset of disease, the exacerbation of intraocular inflammation, and delayed resolution. Suppression of CD59 was only effective when the Abs and ODNs were given before the onset of disease. The most profound effect on the disease was observed when a mixture of Crry and CD59 mAbs or AS-ODNs was administered. A similar effect was observed with a combination of Crry and CD59 small interfering RNA. There was no permanent histologic damage to ocular tissue after the inflammation cleared in these animals. Increased complement activation as determined by increased deposition of C3, C3 activation fragments, and membrane attack complex was observed in the eyes of Lewis rats when the function and/or expression of Crry and CD59 was suppressed. Thus, our results suggest that various ocular tissues up-regulate the expression of Crry and CD59 to avoid self-injury during autoimmune uveitis and that these CRPs play an active role in the resolution of EAAU by down-regulating complement activation in vivo.

The complement system plays a critical role in the development of experimental autoimmune anterior uveitis.

PURPOSE: The role of complement in ocular autoimmunity was explored in a experimental autoimmune anterior uveitis (EAAU) animal model. METHODS: EAAU was induced in Lewis rats by immunization with bovine melanin-associated antigen. Complement activation in the eye was monitored by Western blot for iC3b. The importance of complement to the development of EAAU was studied by comparing the course of intraocular inflammation in normal Lewis rats (complement-sufficient) with cobra venom factor-treated rats (complement-depleted). Eyes were harvested from both complement-sufficient and complement-depleted rats for mRNA and protein analysis for IFN-gamma, IL-10, and interferon-inducible protein (IP)-10. Intracellular adhesion molecule (ICAM)-1 and leukocyte-endothelial cell adhesion molecule (LECAM)-1 were detected by immunofluorescent staining. OX-42 was used to investigate the importance of iC3b and CR3 interaction in EAAU. RESULTS: There was a correlation between ocular complement activation and disease progression in EAAU. The incidence, duration, and severity of disease were dramatically reduced after active immunization in complement-depleted rats. Complement depletion also completely suppressed adoptive transfer EAAU. The presence of complement was critical for local production of cytokines (IFN-gamma and IL-10), chemokines (IP-10), and adhesion molecules (ICAM-1 and LECAM-1) during EAAU. Furthermore, intraocular complement activation, specifically iC3b production and engagement of complement receptor 3 (CR3), had a significant impact on disease activity in EAAU. CONCLUSIONS: The study provided the novel finding that complement activation plays a central role in the pathogenesis of ocular autoimmunity and may serve as a potential target for therapeutic intervention.

Anti-inflammatory effects of specific cyclooxygenase 2,5-lipoxygenase, and inducible nitric oxide synthase inhibitors on experimental autoimmune anterior uveitis (EAAU).

PURPOSE: Inflammation, in general, causes the release of a variety of inflammatory mediators that in turn induce cyclooxygenase (COX) 2, nitric oxide synthase (iNOS) and 5-lipoxygense (LP) synthesis, producing large amounts of inflammatory prostaglandins (PG), nitric oxide (NO), and leukotriene (LT) B4. Therefore, inhibition of these enzymes may abrogate intraocular inflammation in experimental autoimmune anterior uveitis (EAAU). METHODS: Lewis rats were immunized with melanin-associated antigen (MAA) isolated from bovine iris and ciliary body. These animals were divided into three groups. The first group of rats received subcutaneous injection of COX 2 inhibitor CS 236 at different time points. The second and third groups of animals received subcutaneous aminoguanidine (AG), an iNOS inhibitor, and nordihydroguaiaretic acid (NDGA), a 5-LP inhibitor, respectively. Control animals received vehicle. Rat eyes were examined daily by slit-lamp biomicroscopy from Day 7 to 30 post injection for uveitis. Animals were also sacrificed at various time points for histologic analysis. RESULTS: Control animals developed severe EAAU in both eyes. The disease started in these animals on Day 12 post immunization and lasted for ten days. Interestingly, CS 236, a potent COX 2 inhibitor, completely abrogated EAAU when the animals were treated daily from the Day 0 to 14 or Day 0 to 20 after MAA injection. Furthermore, daily CS 236 treatment after the onset of EAAU (Day 14-20) significantly reduced the severity (both clinical and histologic) of EAAU and shortened the duration of disease. iNOS inhibitor (AG) and 5-LP inhibitor (NDGA) partially attenuated EAAU. CONCLUSIONS: Our results show that EAAU was partially attenuated by AG and NDGA. Interestingly, CS 236, a potent COX 2 inhibitor, completely inhibited EAAU in male Lewis rats most likely by inhibiting the initial phase and onset of the disease.

Role of complement and complement membrane attack complex in laser-induced choroidal neovascularization.

Choroidal neovascularization (CNV), or choroidal angiogenesis, is the hallmark of age-related macular degeneration and a leading cause of visual loss after age 55. The pathogenesis of new choroidal vessel formation is poorly understood. Although inflammation has been implicated in the development of CNV, the role of complement in CNV has not been explored experimentally. A reliable way to produce CNV in animals is to rupture Bruch's membrane with laser photocoagulation. A murine model of laser-induced CNV in C57BL/6 mice revealed the deposition of C3 and membrane attack complex (MAC) in the neovascular complex. CNV was inhibited by complement depletion using cobra venom factor and did not develop in C3(-/-) mice. Anti-murine C6 Abs in C57BL/6 mice inhibited MAC formation and also resulted in the inhibition of CNV. Vascular endothelial growth factor, TGF-beta2, and beta-fibroblast growth factor were elevated in C57BL/6 mice after laser-induced CNV; complement depletion resulted in a marked reduction in the level of these angiogenic factors. Thus, activation of complement, specifically the formation of MAC, is essential for the development of laser- induced choroidal angiogenesis in mice. It is possible that a similar mechanism may be involved in the pathophysiology of other angiogenesis essential diseases.

Type I collagen is the autoantigen in experimental autoimmune anterior uveitis.

This study was undertaken to identify and characterize the Ag responsible for the induction of experimental autoimmune anterior uveitis (EAAU). Melanin-associated Ag isolated from bovine iris and ciliary body was digested with the proteolytic enzyme V8 protease to solubilize the proteins and the pathogenic protein was purified to homogeneity. Lewis rats were sensitized to various fractions and investigated for the development of anterior uveitis and an immune response to the purified Ag. The uveitogenic Ag had a mass of 22 kDa (SDS-PAGE) and an isoelectric point of 6.75. The N-terminal amino acid sequence of this protein demonstrated 100% homology with the bovine type I collagen alpha-2 chain starting from amino acid 385 and will be referred to as CI-alpha2 (22 kDa). Animals immunized with bovine CI-alpha2 (22 kDa) developed both cellular and humoral immunity to the Ag. They developed anterior uveitis only if the CI-alpha2 chain underwent proteolysis and if the bound carbohydrates were intact. EAAU induced by CI-alpha2 (22 kDa) can be adoptively transferred to naive syngenic rats by primed CD4(+) T cells. EAAU could not be induced by the adoptive transfer of sera obtained from animals immunized with CI-alpha2 (22 kDa). The alpha-1 and alpha-2 chains (intact or proteolytically cleaved) of type I collagen from calfskin were not pathogenic. Although human anterior uveitis has been historically characterized as a collagen disease, this is first time collagen has been directly identified as the target autoantigen in uveitis.