Unilateral conjunctival Classic Kaposi Sarcoma following a COVID 19 booster.

Purpose: We describe a case of Classic Kaposi's sarcoma in a functionally monocular patient following a COVID19 vaccine booster and provide compelling evidence that suggests the booster was a relevant co-factor in the initiation of the disease process. Observations: The patient presented with red, irritated conjunctival area described as "bubbling" in her right eye. While her past medical history includes hypercholesterolemia and hypertension, she had no history of a compromised immune system. Her ophthalmologic history is more complex including treatment for glaucoma. The patient has 20/20 uncorrected vision OD and LP OS. Due to her ocular co-morbidities, the patient initially received interferon alpha 2-B qid for 6 weeks. However, topical therapy failed to decrease the size of the conjunctival lesions. After referral to Radiation Oncology, the right eye/orbit was treated with electron beam therapy for 1 month which caused a marked decrease in the size and vascularity of the conjunctival lesions. A slow improvement continued during followup. Conclusion and importance: In that the vaccine booster preceded the cancer, it appears etiologic to the appearance of Kaposi's sarcoma. The patient's monocular vision and glaucoma complicated her treatment. This case expands on current concepts of cofactors needed for the development of Kaposi's sarcoma in that vaccine booster administration was relevant to tumor progression and both clinical and mechanistic evidence is presented to support this hypothesis.

The Antiangiogenic Effect and Ocular Pharmacology of Novel Modified Nonsteroidal Anti-Inflammatory Drugs in the Treatment of Oxygen-Induced Retinopathy.

Purpose: To evaluate the hypothesis that 3 novel compounds, OXT-328, Q-922, and CL-717 show efficacy in the treatment of oxygen-induced retinopathy (OIR) and whether or not their route of administration is intravitreal, topical, or systemic. Methods: The OIR mouse model, characterized by an avascular area (AVA) and a neovascular area (NVA) of the retina, was used to study retinopathy of prematurity and other retinal diseases characterized by abnormal vessel growth. We measured the effect of our compounds on both the AVA and NVA in whole mounts of mouse retinal tissue. We also evaluated their ability to prevent new vessel formation in chicken chorioallantoic membranes (CAMs). Finally, we measured the in vitro uptake and biodistribution of topically applied CL-717 in human eye explants. Results: In mice with OIR, compared to controls, a single intravitreal administration of Q-922 or OXT-328 significantly reduced both AVA and NVA. CL-717 administered as eye drops over 5 days also reduced AVA and NVA, whereas OXT-328 eye drops had no effect. Q-922 given intraperitoneal (150 mg/kg/day × 5 days) reduced AVA and NVA. Remarkably, explanted human eyes bathed in CL-717 show rapid uptake and biodistribution in ocular tissues. In the chicken CAM model, all 3 compounds reduced the formation of new blood vessels by about one-third. No side effect in mice was observed, except for mild ocular surface irritation with Q-922. Conclusions: Systemic administration of Q-922 or topical administration of CL-717 holds particular promise for a simplified treatment of proliferative retinopathies without the necessity of intravitreal injections.

Phosphosulindac (OXT-328) prevents and reverses chemotherapy induced peripheral neuropathy in mice.

Background: Chemotherapy-induced peripheral neuropathy (CIPN), a side effect of chemotherapy, is particularly difficult to treat. We explored whether phosphosulindac (PS), a modified NSAID, could treat CIPN. Methods: CIPN was induced in male C57BL/6 J mice by paclitaxel, vincristine or oxaliplatin. Mechanical allodynia was measured with the von Frey test and cold allodynia with the acetone test. To determine the preventive effect of PS, it was administered 2 days before the induction of CIPN. Mouse Lewis lung carcinoma xenografts were used to determine if PS altered the chemotherapeutic efficacy of paclitaxel. Cultured cell lines were used to evaluate the effect of PS on neuroinflammation. Results: Treatment with each of the three chemotherapeutic agents used to induce CIPN lowered the mechanical allodynia scores by 56 to 85% depending on the specific agent. PS gel was applied topically 3x/day for 16-22 days to the hind paws of mice with CIPN. This effect was dose-dependent. Unlike vehicle, PS returned mechanical allodynia scores back to pre-CIPN levels. PS had a similar effect on paclitaxel-induced CIPN cold allodynia. Sulindac, a metabolite of PS, had no effect on CIPN. PS significantly prevented CIPN compared to vehicle. Given concomitantly with paclitaxel to mice with lung cancer xenografts, PS relieved CIPN without affecting the anticancer effect of paclitaxel. The enantiomers of PS were equally efficacious against CIPN, suggesting the therapeutic suitability of the racemate PS. There were no apparent side effects of PS. PS suppressed the levels of IL-6, IL-10, CXCL1, and CXCL2 induced by paclitaxel in a neuroblastoma cell line, and macrophage activation to the M1 proinflammatory phenotype. Conclusion: Topically applied PS demonstrated broad therapeutic and preventive efficacy against CIPN, preserved the anticancer effect of paclitaxel, and was safe. Its anti-CIPN effect appears to be mediated, in part, by suppression of neuroinflammation. These data support further evaluation of topical PS for the control of CIPN.

Non-contact terahertz spectroscopic measurement of the intraocular pressure through corneal hydration mapping.

Elevated intraocular pressure (IOP) results in endothelial layer damage that can induce corneal hydration perturbations. We investigated the potential of terahertz spectroscopy in measuring the IOP levels through mapping corneal water content. We controlled the IOP levels in ex vivo rabbit and porcine eye samples while monitoring the change in corneal hydration using a terahertz time-domain spectroscopy (THz-TDS) scanner. Our results showed a statistically significant increase in the THz reflectivity between 0.4 and 0.6 THz corresponding to the increase in the IOP. Endothelial layer damage was confirmed using scanning electron microscopy (SEM) of the corneal biopsy samples. Our empirical results indicate that the THz-TDS can be used to track IOP levels through the changes in corneal hydration.

NSAID-induced corneal melt: Clinical importance, pathogenesis, and risk mitigation.

Corneal melt, an ophthalmological condition in which corneal epithelium is lost accompanied by thinning of the corneal stroma, can lead to corneal perforation and cause loss of vision. Corneal melt is the most serious side effect of topical nonsteroidal anti-inflammatory drugs (NSAIDs), one of the topical treatments of ocular inflammation. NSAID-induced corneal melt (NICM), initially doubted, is real, having been reported by multiple groups. NICM is induced by all but one of the approved ocular NSAIDs and occurs usually in patients whose cornea is compromised by ocular surgery, diabetes, or autoimmune diseases. Its true incidence, most likely low, remains unknown. NSAID dose and duration of treatment may be important for NICM. NICM appears to evolve in two stages: the epithelial stage-marked by a corneal epithelial defect, reduced eicosanoid levels, leukocyte infiltration, and matrix metalloproteinase-facilitated desquamation-and the stromal stage, characterized by degradation of stromal collagen by activated matrix metalloproteinases. Awareness of this ominous side effect, its risk factors, and the need for prompt action once diagnosed, including NSAID discontinuation, will help mitigate the risk of NICM. Further understanding of NICM and development of efficacious treatments or safer alternatives should help eliminate this rare, but severe, side effect of ocular NSAIDs.

Relationship between sleep position and glaucoma progression.

PURPOSE OF REVIEW: As humans spend a considerable portion of life in the horizontal position, it is vital to better understand the effect of sleep position on glaucoma. RECENT FINDINGS: The mean positional increase from the supine position to the lateral decubitus position (LDP) in recent literature is less than 2 mmHg for each eye in its dependent position and less than 1 mmHg in the nondependent position. The right LDP is most commonly favored sleeping position. Some evidence suggests that the positional increases persist and so could lead to worse glaucomatous progression in the dependent eye. However, multiple studies failed to find a strong association. Ideally future research will identify risk factors for higher positional increases to identify patients who may benefit from a change in sleep position. To date, medications and argon laser trabeculoplasty have been ineffective in blunting the positional increase, although glaucoma surgery does reduce it. Raising the head of the bed has been linked with blunting the increase as well. SUMMARY: Certain sleeping positions appear to be associated with higher intraocular pressure, although the association between sleep position and glaucoma progression is not as clear.

A New Rabbit Model of Chronic Dry Eye Disease Induced by Complete Surgical Dacryoadenectomy.

Purpose/Aim: Dry eye disease (DED), common and suboptimally treated, is in need of novel animal models to understand its pathophysiology and assess the efficacy and other parameters of new pharmacological agents for its treatment. The more than 10 rabbit models of DED described to date have significant limitations including induction of mild disease, lack of consistency, and off-target effects when chemical agents are used for disease induction. Our aim was to develop a new model of chronic DED in rabbits that overcomes the limitations of existing models. MATERIALS AND METHODS: We performed a complete surgical resection of all orbital lacrimal glands (LGs; dacryoadenectomy) in normal adult New Zealand White rabbits. One week after removal of the nictitating membrane, we surgically removed the orbital superior LG, followed by removal of the palpebral superior LG, and finally removal of the inferior LG. Surgery was performed under anesthesia, required about 1 h/eye, and was well-tolerated. RESULTS: Dacryoadenectomy induced severe DED, evidenced by >90% reduction in the tear break up time test, 50% reduction in the Schirmer tear test, 10% increase in tear osmolarity, and a marked increase in the rose bengal staining score. DED was sustained and essentially unchanged for the eight weeks of observation. Sham-operated rabbits showed no such changes, with the exception of a non-significant and transient reduction in the tear break up time test, a response to ocular surgery. CONCLUSIONS: This model of stable, chronic, predominantly aqueous-deficient DED recapitulates key clinical and histological features of human DED and is suitable for the study of ocular surface homeostasis, of the pathophysiology of DED, and of the efficacy of candidate drugs for DED treatment.

Improved refractive outcomes of postgraduate year 4 cataract surgery after implementing a stepwise biometry lecture series reinforced by self-assessment at a teaching program.

PURPOSE: To determine whether a structured biometry course improves refractive outcomes of resident phacoemulsification. SETTING: Northeast Veterans Administration Hospital, Northport, New York, USA. DESIGN: Retrospective case study. METHODS: Phacoemulsification surgeries performed by residents before and after a biometry curriculum were reviewed. The inclusion criterion was phacoemulsification performed by residents. Patients with fewer than 3 months of follow-up were excluded. The main outcome measure-the mean absolute difference between the target and final refraction-was compared using a linear mixed model. RESULTS: Phacoemulsification surgeries performed by 4 residents before (n = 223) and by 4 residents after (n = 242) a biometry curriculum was implemented were reviewed. All measured preoperative factors were similar in both groups, including age, visual acuity, axial length, steep and flat keratometry values, astigmatism, anterior chamber depth, and lens thickness. Before the biometry course was instituted, 10% of patients had a mean absolute difference of less than 0.25 diopter (D); the percentage was 35% afterward. The mean absolute difference was less than 0.50 D in 40% before the curriculum was initiated and 70% after. The mean absolute difference was less than 1.00 D in 75% before the curriculum was initiated versus 94% after (all P < .05). The corrected distance visual acuities were similar in both groups, with 83% and 80%, respectively, having an acuity of at least 20/25 (P > .05). CONCLUSION: Residents' refractive predictions significantly improved after a formal biometry curriculum, showing that improvements in resident surgical outcomes are possible with structured curriculums reinforcing outcome measures. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned.

Review and meta-analysis of ab-interno trabeculectomy outcomes.

We analysed all of the PubMed publications on ab-interno trabeculectomy (AIT) with the Trabectome (Neomedix, Irvine, California, USA) to determine the reduction in intraocular pressure (IOP) and medications following the procedure. For IOP outcomes, PubMed was searched for 'trabectome', 'ab interno trabeculotomy' and 'ab interno trabeculectomy' and all available papers retrieved. The meta-analysis used a random-effects model to achieve conservative estimates and assess statistical heterogeneity. To investigate complications, we included all abstracts from the American Glaucoma Society, American Academy of Ophthalmology, American Society of Cataract and Refractive Surgery and the Association for Research in Vision and Ophthalmology. The overall arithmetic mean baseline IOP for standalone Trabectome was 26.71±1.34 mm Hg and decreased by 10.5±1.9 mm Hg (39% decrease) on 0.99±0.54 fewer medications. Defining success as IOP ≤21 with a 20% decrease while avoiding reoperation, the overall average success rate after 2 years was 46±34%. For combined phacoemulsification-Trabectome, the baseline IOP of 21±1.31 mm Hg decreased by 6.24±1.98 mm Hg (27% decrease) on 0.76±0.35 fewer medications. The success rate using the same definition at 2 years was 85±7%. The weighted mean IOP difference from baseline to study endpoint was 9.77 mm Hg (95% CI 8.90 to 10.64) standalone and 6.04 mm Hg (95% CI 4.95 to 7.13) for combined cases. Despite heterogeneity, meta-analysis showed significant and consistent decrease in IOP and medications from baseline to end point in AIT and phaco-AIT. The rate of visually threatening complications was <1%. On average, trabectome lowers the IOP by approximately 31% to a final IOP near 15 mm Hg while decreasing the number of medications by less than one, with a low rate of serious complications. After 2 years, the overall average success rate is 66%.

The use of endoscopic cyclophotocoagulation for moderate to advanced glaucoma.

Endoscopic Cyclophotocoagulation (ECP) is a glaucoma surgery designed to reduce the intraocular pressure (IOP) by partially ablating the ciliary processes to decrease aqueous humour production and secretion. The aim of this paper is to review the literature regarding the background, indications and results of the surgery. Although there are case reports of visually devastating complications, including persistent hypotony and phthisis, the use of ECP is often reported in eyes with advanced diseases. When compared with both trabeculectomy and aqueous shunt implantation, the visual outcomes were better with ECP while the IOP outcomes were very similar. The evidence supports ECP as a very effective surgical option in recalcitrant glaucoma while some evidence supports its safety for use as a primary procedure.

Optical coherence tomography shape analysis of the peripapillary retinal pigment epithelium layer in presumed optic nerve sheath meningiomas.

BACKGROUND: Geometric morphometrics (GM) was used to compare the shape of the peripapillary retinal pigment epithelium-Bruch's membrane (ppRPE) layer imaged on spectral domain optical coherence tomography (SD-OCT) of patients with presumed optic nerve sheath meningiomas (pONSM) and normal subjects. METHODS: We compared 2 groups: 30 normals to 10 patients (11 eyes) with pONSM. We digitized 20 equidistant semi-landmarks on OCT images of the ppRPE-layer, spanning 2500 µm on each side of the neural canal opening (NCO). Data were analyzed using standard GM techniques including a generalized least squares Procrustes superimposition, principal component analysis (PCA), thin-plate spline, and permutation statistical analysis to evaluate differences in shape. We also analyzed other variables with respect to shape including tumor size-proximity to the globe, age, retinal nerve fiber layer, and optic disc height. RESULTS: All pONSM patients were female (age 37-66 years); 10 had unilateral and 1 had bilateral optic nerve involvement. Ten of the eyes had optic disc edema at presentation, 4 went on to develop shunt vessels, and 4 had optic atrophy. The ppRPE-layer bordering the NCO in normals is V-shaped pointing away from the vitreous; the ppRPE-layer in pONSM is indented causing an inverted-U shaped deformation skewed nasally toward the vitreous. PCA showed a significant difference between normals and pONSM (permutation, n = 10,000, P = 0.001). The size and proximity of the tumor to the globe correlates with the shape of the ppRPE-layer (r = 0.75, P = 0.04). Correlation between shape variables and RNFL thickening (r = 0.51), optic disc height (r = 0.67), and age (r = 0.67) were not statistically significant. CONCLUSION: The shape of the RPE layer in pONSM is characterized by an inverted-U shape or indentation that differs significantly from normals. It is indistinguishable from the shape we previously reported in papilledema and is not caused by disc edema. The mechanism in pONSM is unknown but may involve a change in the compliance of the nerve and/or localized sequestration of cerebrospinal fluid in the distal optic nerve sheath.

Asymptomatic peripapillary subretinal hemorrhage: a study of 10 cases.

BACKGROUND: Peripapillary subretinal hemorrhage (PSH) is often found together with optic disc drusen, optic disc edema, peripapillary subretinal neovascular membranes, vitreous traction, and bleeding diatheses. Previous reports have stated that such optic disc hemorrhages are associated with intrapapillary bleeding largely in patients of Asian origin who are visually symptomatic from this process. We have encountered patients with PSH who have clinical features that differ from those described in these reports. METHODS: This is a retrospective observational case series. Medical records of 10 patients with isolated peripapillary subretinal hemorrhages were reviewed for clinical characteristics and ancillary testing, including demographics, history, complete eye examination, visual fields, fundus photos, ultrasound, and fluorescein angiography (four patients) at presentation and follow-up. We excluded patients with drusen, neovascular membranes, disc edema, and intrapapillary hemorrhages. RESULTS: There were 10 patients, all white women without visual symptoms, who had isolated, monocular, nasal, or superonasal peripapillary subretinal hemorrhage, a dysplastic crowded-tilted optic disc, myopia, and normal visual function. The hemorrhages resolved without sequelae over 3-6 months. The findings were frequently discovered on routine examination and suspected of representing papilledema. CONCLUSIONS: We have described a benign syndrome of isolated PSH in crowded and tilted optic discs in myopic eyes of white women. The PSHs do not cause visual symptoms and resolve spontaneously. We propose that an interplay of ocular motor forces, scleral thinning, and vitreopapillary traction acting on a morphologically vulnerable optic disc explains these hemorrhages.

A family with Axenfeld-Rieger syndrome and Peters Anomaly caused by a point mutation (Phe112Ser) in the FOXC1 gene.

PURPOSE: Mutations of the forkhead transcription factor gene FOXC1 result in anterior segment anomalies. No description of the spectrum of defects resulting from a single point mutation of this gene exists in the ophthalmology literature. We have screened all available patients with Axenfeld-Rieger genes (PITX2 and FOXC1). In this report, we clinically characterize the spectrum of ocular and systemic manifestations in one family resulting from a previously reported point mutation (Phe112Ser) in FOXC1. DESIGN: Observational case series. METHODS: Ten members of a multigenerational family were examined for signs of glaucoma, anterior segment abnormalities, and systemic features of Axenfeld-Rieger syndrome. The examinations were performed in an ophthalmology examination room or in the patients' homes. Blood was obtained from 10 members and screened for mutations in FOXC1 using direct DNA sequencing. RESULTS: A single mutation causing a T to C change in codon 112 (Phe112Ser) of FOXC1 was present in six members of the family. Five of these six patients were examined and all demonstrated anterior segment anomalies. One patient had Axenfeld anomaly, one had Rieger syndrome, and one had both Axenfeld anomaly and Peters anomaly. Additionally, some members demonstrated cardiac abnormalities, which may be secondary to their FOXC1 mutation. CONCLUSIONS: A wide spectrum of clinical phenotypes can result from a single point mutation of FOXC1. This report confirms that Rieger syndrome (with dental and facial abnormalities) can be caused by a mutation in FOXC1. It is also the first report of Peters anomaly being caused by a FOXC1 mutation.