Longitudinal analysis of clinical and laboratory biomarkers in a patient with familial lecithin: Cholesterol acyltransferase deficiency (FLD) and accelerated eGFR decline: A case study.

Familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) is an ultra-rare autosomal recessive disease characterized by very low HDL-C levels, corneal opacity, anemia, and progressive renal disease. The rate and severity of renal disease are variable across FLD patients and the biomarkers and risk factors for disease progression are poorly understood. Here we report a 30 year-long comparative analysis of the clinical and laboratory biomarkers in an FLD patient with accelerated renal decline, who underwent 2 kidney and one liver transplantations. Results show that elevated TG and non-HDL-C levels may promote the formation of LpX and accelerate renal function decline, whereas markers of anemia may be early predictors. Conversely, corneal opacity progresses at a steady rate and does not correlate with lipid, hematologic, or renal biomarkers. Our study suggests that monitoring of markers of anemia may aid the early detection and timely management of kidney disease with conservative therapies. Furthermore, it suggests that controlling hypercholesterolemia and hypertriglyceridemia may help improve renal disease prognosis.

Outcomes of resident physician-performed cataract surgery in a diverse veterans affairs health system population.

Purpose: To evaluate visual acuity (VA) outcomes and complications from resident physician-performed cataract surgery in a diverse Veterans Affairs Hospital population. Methods: A retrospective chart review was conducted for patients who underwent cataract surgery performed by resident physicians from 01/01/2013 to 12/31/2015 at the Veterans Affairs Medical Center. Intraoperative and postoperative clinical information, best-corrected VA (BCVA) (1 day, months 1, 2-3, and 6), and surgery complications were extracted. Univariable and multivariable linear regression models were performed for risk factors of BCVA change. Results: This study included 1183 patients, with mean (SD) age of 70.8 (9.3) years. 1154 (97.5%) were males, 493 (41.7%) African-American, and 681 (57.6%) Caucasian. The mean (SD) VA in logMAR was 0.69 (0.74) at baseline, improved to 0.19 (0.36) at 1 month, 0.16 (0.34) at 2-3 months, and 0.14 (0.36) at 6 months. 1080 (91.3%) patients experienced VA improvement from baseline and 1023 (86.5%) patients achieved at least 20/40 BCVA at 1 month. There were 86 (7.3%) complications, most commonly including 47 (4.0%) posterior capsular tears and 64 (5.4%) vitreous loss. In multivariable analysis, younger age (P < 0.0001), worse baseline VA (P < 0.0001), and absence of iris prolapse (P < 0.001) were significantly associated with greater improvement in VA at 1 month. Conclusion: In a diverse VAMC, resident-performed cataract surgeries achieved significant improvement in VA with a cumulative complication rate lower than previously reported. Resident physician education may benefit from specific focus on prevention of iris prolapse and better incision construction during surgery as these intraoperative events often led to delayed stabilization of visual outcome beyond 1 month.

Topical ophthalmic anesthetics for corneal abrasions.

BACKGROUND: Despite potential analgesic benefits from topical ophthalmic amides and esters, their outpatient use has become of concern because of the potential for abuse and ophthalmic complications. OBJECTIVES: To assess the effectiveness and safety of topical ophthalmic anesthetics compared with placebo or other treatments in persons with corneal abrasions. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; Embase.com; Latin American and Caribbean Health Sciences (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), without restriction on language or year of publication. The search was performed on 10 February 2023. SELECTION CRITERIA: We included randomized controlled trials (RCTs) of topical ophthalmic anesthetics alone or in combination with another treatment (e.g. nonsteroidal anti-inflammatory drugs (NSAIDs)) versus a non-anesthetic control group (e.g. placebo, non-treatment, or alternative treatment). We included trials that enrolled participants of all ages who had corneal abrasions within 48 hours of presentation. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. MAIN RESULTS: We included nine parallel-group RCTs with a total of 556 participants (median number of participants per study: 45, interquartile range (IQR) 44 to 74), conducted in eight countries: Australia, Canada, France, South Korea, Turkey, New Zealand, UK, and USA. Study characteristics and risk of bias Four RCTs (314 participants) investigated post-traumatic corneal abrasions diagnosed in the emergency department setting. Five trials described 242 participants from ophthalmology surgery centers with post-surgical corneal defects: four from photorefractive keratectomy (PRK) and one from pterygium surgery. Study duration ranged from two days to six months, the most common being one week (four RCTs). Treatment duration ranged from three hours to one week (nine RCTs); the majority were between 24 and 48 hours (five RCTs). The age of participants was reported in eight studies, ranging from 17 to 74 years of age. Only one participant in one trial was under 18 years of age. Of four studies that reported funding sources, none was industry-sponsored. We judged a high risk of bias in one trial with respect to the outcome pain control by 48 hours, and in five of seven trials with respect to the outcome complications at the furthest time point. The domain for which we assessed studies to be at the highest risk of bias was missing or selective reporting of outcome data. Findings The treatments investigated included topical anesthetics compared with placebo, topical anesthetic compared with NSAID (post-surgical cases), and topical anesthetics plus NSAID compared with placebo (post-surgical cases). Pain control by 24 hours In all studies, self-reported pain outcomes were on a 10-point scale, where lower numbers represent less pain. In post-surgical trials, topical anesthetics provided a moderate reduction in self-reported pain at 24 hours compared with placebo of 1.28 points on a 10-point scale (mean difference (MD) -1.28, 95% confidence interval (CI) -1.76 to -0.80; 3 RCTs, 119 participants). In the post-trauma participants, there may be little or no difference in effect (MD -0.04, 95% CI -0.10 to 0.02; 1 RCT, 76 participants). Compared with NSAID in post-surgical participants, topical anesthetics resulted in a slight increase in pain at 24 hours (MD 0.82, 95% CI 0.01 to 1.63; 1 RCT, 74 participants). One RCT compared topical anesthetics plus NSAID to placebo. There may be a large reduction in pain at 24 hours with topical anesthetics plus NSAID in post-surgical participants, but the evidence to support this large effect is very uncertain (MD -5.72, 95% CI -7.35 to -4.09; 1 RCT, 30 participants; very low-certainty evidence). Pain control by 48 hours Compared with placebo, topical anesthetics reduced post-trauma pain substantially by 48 hours (MD -5.68, 95% CI -6.38 to -4.98; 1 RCT, 111 participants) but had little to no effect on post-surgical pain (MD 0.41, 95% CI -0.45 to 1.27; 1 RCT, 44 participants), although the evidence is very uncertain. Pain control by 72 hours One post-surgical RCT showed little or no effect of topical anesthetics compared with placebo by 72 hours (MD 0.49, 95% CI -0.06 to 1.04; 44 participants; very low-certainty evidence). Proportion of participants with unresolved epithelial defects When compared with placebo or NSAID, topical anesthetics increased the number of participants without complete resolution of defects in trials of post-trauma participants (risk ratio (RR) 1.37, 95% CI 0.78 to 2.42; 3 RCTs, 221 participants; very low-certainty evidence). The proportion of placebo-treated post-surgical participants with unresolved epithelial defects at 24 to 72 hours was lower when compared with those assigned to topical anesthetics (RR 0.14, 95% CI 0.01 to 2.55; 1 RCT, 30 participants; very low-certainty evidence) or topical anesthetics plus NSAID (RR 0.33, 95% CI 0.04 to 2.85; 1 RCT, 30 participants; very low-certainty evidence). Proportion of participants with complications at the longest follow-up When compared with placebo or NSAID, topical anesthetics resulted in a higher proportion of post-trauma participants with complications at up to two weeks (RR 1.13, 95% CI 0.23 to 5.46; 3 RCTs, 242 participants) and post-surgical participants with complications at up to one week (RR 7.00, 95% CI 0.38 to 128.02; 1 RCT, 44 participants). When topical anesthetic plus NSAID was compared with placebo, no complications were reported in either treatment arm up to one week post-surgery (risk difference (RD) 0.00, 95% CI -0.12 to 0.12; 1 RCT, 30 participants). The evidence is very uncertain for safety outcomes. Quality of life None of the included trials assessed quality of life outcomes. AUTHORS' CONCLUSIONS: Despite topical anesthetics providing excellent pain control in the intraoperative setting, the currently available evidence provides little or no certainty about their efficacy for reducing ocular pain in the initial 24 to 72 hours after a corneal abrasion, whether from unintentional trauma or surgery. We have very low confidence in this evidence as a basis to recommend topical anesthetics as an efficacious treatment modality to relieve pain from corneal abrasions. We also found no evidence of a substantial effect on epithelial healing up to 72 hours or a reduction in ocular complications when we compared anesthetics alone or with NSAIDs versus placebo.

Severe Mpox Infection of the Eye and Periocular Region.

Mpox is an emerging zoonotic infection with potentially severe ocular and periocular consequences, particularly in immunocompromised patients. This report summarizes 2 cases of fulminant mpox presenting in patients with AIDS. In the first case, confluent lesions resulted in orbital compartment syndrome and total eyelid necrosis. In the second case, eyelid involvement was accompanied by corneal melt and perforation. Despite aggressive medical and surgical treatment, both patients developed permanent loss of vision and ultimately expired.

Corneal Culture and Antibiotic Susceptibility Results for Microbial Keratitis in the Mid-Atlantic Region of the United States, 2016 to 2020.

OBJECTIVE: To examine the microbial distribution and antimicrobial susceptibility of culture-positive microbial keratitis at a large tertiary referral center in the mid-Atlantic region of the United States. METHODS: Retrospective review of culture-positive microbial keratitis cases at the Wilmer Eye Institute from 2016 through 2020. RESULTS: Of the 474 culture-positive microbial keratitis cases, most were bacterial (N=450, 94.9%), followed by fungal (N=48, 10.1%) and Acanthamoeba keratitis (N=15, 3.1%). Of the 450 bacterial isolates, 284 (69.5%) were gram-positive organisms, whereas 157 (28.4%) were gram-negative organisms. The most common bacterial species isolated was coagulase-negative Staphylococcus spp (N=154, 24.8%), and the most common gram-negative isolate was Pseudomonas aeruginosa (N=76, 12.3%). Among fungi, the most common isolates were Candida (N=25, 45.4%), whereas Fusarium (N=6, 10.9%) and Aspergillus (N=3, 5.5%) were less common. Of the 217 bacterial isolates tested for erythromycin susceptibility, 121 (55.7%; ∼60% of coagulase-negative staphylococci and corynebacteria tested) showed resistance to erythromycin. CONCLUSIONS: Microbial keratitis in the Baltimore Mid-Atlantic region of the United States is most commonly caused by bacteria, with fungi and acanthamoeba being less common. Gram-positive bacterial infections predominate. Among fungal keratitis cases, Candida species are more commonly encountered than are filamentous species. Use of erythromycin as infection prophylaxis should be reexamined. Findings from our study may guide empiric treatment in this geographic region.

Cataracts in setting of multisystem inflammation after COVID-19 vaccination.

Purpose: To describe a unique case of bilateral cataract formation in the setting of multisystem inflammation after the 1st dose of the BNT162b2 mRNA COVID-19 vaccination. Observations: A previously healthy 20-year-old male developed intumescent bilateral cataracts leading to visual decline from 20/20 to 20/300-20/400 in each eye, likely from systemic inflammation after vaccination. Conclusion and importance: This is the first reported case of cataract formation following a COVID-19 vaccine. While ocular adverse effects associated with COVID-19 vaccination are rare, it is important to raise awareness of these entities amongst medical providers as the COVID-19 pandemic continues and vaccinations become widespread.

Corneal Edema and Keratoplasty: Risk Factors in Eyes With Previous Glaucoma Drainage Devices.

PURPOSE: To assess risk factors contributing to corneal decompensation following glaucoma drainage device (GDD) implantation. DESIGN: Retrospective case control study. METHODS: Records of 1610 eyes that underwent GDD implantation between June 1, 2009, and April 1, 2020, at the Johns Hopkins Wilmer Eye Institute were reviewed. Seventy-nine eyes (5%) developed corneal decompensation, of which 46 underwent keratoplasty. These 79 cases were matched with 220 controls. Cox proportional hazard models with robust standard error estimates to account for clustering at the matched-pair level were used to assess risk factors for corneal decompensation. Kaplan-Meier survival analysis analyzed time to corneal decompensation. RESULTS: The mean (SD) age of cases and controls was 68 (12.3) and 60.5 (15.9) years, respectively. The mean time from GDD implantation to corneal decompensation was 32 months, and the cumulative probability of developing decompensation at 3, 6, and 9 years was 4.7%, 9.2%, and 14.8%, respectively. Final visual outcomes in cases were worse, with a final mean ± SD visual acuity (logMAR) of 1.96±1.25 relative to a mean±SD visual acuity of 1.11±1.36 in controls (P < .001). In the multivariable model, significant risk factors for corneal decompensation were increased age (adjusted hazard ratio [AHR] 1.39, 95% CI 1.18, 1.63; P ≤ .001), history of Fuchs dystrophy or iridocorneal endothelial syndrome (AHR 9.18, 95% CI 5.35, 15.74; P ≤ .001), and postoperative complications such as hypotony (AHR 3.25, 95% CI 1.85, 5.72; P ≤ .001) and tube-cornea touch (AHR 6.37, 95% CI 3.77, 10.75; P ≤ .001). CONCLUSIONS: The risk of postoperative corneal decompensation is persistent over time. Patients receiving GDDs, particularly those with advanced age, preexisting corneal pathology, and postoperative complications, should be counseled regarding their increased risk for corneal decompensation.

A 15-YEAR-OLD BOY WITH PROTRACTED VISION LOSS FROM ACUTE POSTERIOR MULTIFOCAL PLACOID PIGMENT EPITHELIOPATHY.

PURPOSE: To present an atypical case of acute posterior multifocal placoid pigment epitheliopathy in a 15 year old treated with immunosuppressive therapy. METHODS: Interventional case report. RESULTS: On initial presentation, the vision was 20/200 in the right eye and 20/300 in the left eye. The posterior poles of both eyes showed numerous creamy-white placoid lesions. Fundus autofluorescence demonstrated hypoautofluorescence lesions with hyperautofluorescence rims, while fluorescein angiography showed early blockage followed by late staining. These findings were consistent with a diagnosis of acute posterior multifocal placoid pigment epitheliopathy. Optical coherence tomography demonstrated outer retinal disruptions and thinning. Due to the severity of his disease, the patient was treated first with oral prednisone and later transitioned to mycophenolate mofetil by 2 months. His poor vision persisted beyond a 5-month follow-up visit despite fading of the lesions and reconstitution of the outer retinal layers and thickness on optical coherence tomography. By 8 months of follow-up, the visual acuity returned to 20/20 bilaterally without any further recurrences. CONCLUSION: Although most patients with acute posterior multifocal placoid pigment epitheliopathy have a relatively short course and recover vision quickly, the use of steroids and immunosuppression may be of benefit for those patients with severe and prolonged visual loss.

The use of self-retained, cryopreserved amniotic membrane for the treatment of Sjögren syndrome: a case series.

PURPOSE: To determine whether signs and symptoms of ocular surface disease improve after placement of a self-retained, cryopreserved amniotic membrane (CAM) in patients with Sjögren syndrome (SS). METHODS: The medical records of SS patients who received a self-retained CAM implant (Prokera or Prokera Slim; TissueTech Inc, Doral, FL) for the treatment of ocular surface disease between August 2012 and August 2016 at a single, large academic institution were reviewed retrospectively. Visual acuity, results of slit-lamp examination of the cornea and conjunctiva, and dry eye symptoms, were evaluated before and after CAM insertion. RESULTS: A total of 6 eyes of 6 patients (all female; mean age, 62.5 ± 13.0 years [range, 49-86 years]) were included. All patients were on topical medications at the time of the study and had signs of ocular surface dryness. There were reductions in corneal and/or conjunctival staining in 5 eyes (83%) after the CAM dissolved. All patients who completed therapy (5/5) experienced a relapse in their signs and symptoms within 1 month of removal of the CAM, with an average time to relapse of 24.6 days. Mean follow-up time was 54.5 days. Foreign body sensation and blurred vision were the most common complaints associated with the CAM implant. CONCLUSIONS: In this small case series, self-retained CAM implantation was found to be beneficial in SS patients with ocular surface disease that is refractory to standard therapies; however, we found that the effects were temporary. Future larger studies are needed to confirm these benefits.

Survey of Ophthalmologists Regarding Practice Patterns for Dry Eye and Sjogren Syndrome.

OBJECTIVE: To survey ophthalmologists about current practice patterns regarding the evaluation of dry eye patients and referrals for a Sjogren syndrome (SS) workup. METHODS: An online survey was sent to ophthalmologists affiliated with the Scheie Eye Institute or Wills Eye Hospital using REDCap in August 2015. Descriptive statistics were used to summarize the data. RESULTS: Four hundred seventy-four survey invitations were sent out and 101 (21%) ophthalmologists completed the survey. The common traditional dry eye test performed was corneal fluorescein staining (62%) and the most common newer dry eye test performed was tear osmolarity (18%). Half of respondents (51%) refer fewer than 5% of their dry eye patients for SS workups, with 18% reporting that they never refer any patients. The most common reasons for referrals included positive review of systems (60%), severe dry eye symptoms (51%) or ocular signs (47%), or dry eye that is refractory to treatment (42%). The majority (83%) felt that there is a need for an evidence-based standardized screening tool for dry eye patients to decide who should be referred for evaluation for SS. CONCLUSIONS: Ophthalmologists continue to prefer the use of traditional dry eye tests in practice, with the most common test being corneal fluorescein staining. There is an underreferral of dry eye patients for SS workups, which is contributing to the continued underdiagnosis of the disease. Most respondents felt that there was a need for an evidence-based standardized screening tool to decide which dry eye patients should be referred for SS evaluations.

Complement C5a receptor knockout has diminished light-induced microglia/macrophage retinal migration.

PURPOSE: The complement system is involved in the pathogenesis of age-related macular degeneration (AMD). Because activated microglia are also associated with AMD, we studied the relationship between complement anaphylatoxin receptors and microglial recruitment. METHODS: We assessed the effect of anaphylatoxin C3a receptor (C3aR) and C5a receptor (C5aR) knockout (KO) on light damage-induced migration of microglia/macrophages into the mouse outer retina via immunofluorescence and real-time quantitative PCR. RESULTS: We found that the mRNA levels of C3, C5, C3aR, C5aR, and two activators of the complement alternative pathway, Cfb and Cfd, were all upregulated after light exposure. Retinal Iba1-positive microglia/macrophages express receptors for C3a and C5a. Light damage increased the number of retinal Iba1-positive cells and the mRNA levels of Iba1. Compared with the wild-type (WT) mice, these increases were attenuated in the C5aR KO mice but not in the C3aR KO mice. CONCLUSIONS: C5aR but not C3aR promoted the recruitment of microglia/macrophages. These divergent properties of complement anaphylatoxins in the light damage model provide a rationale for testing the differential effects of these receptors in additional retinal and neurodegeneration models.

NR4A nuclear receptors support memory enhancement by histone deacetylase inhibitors.

The formation of a long-lasting memory requires a transcription-dependent consolidation period that converts a short-term memory into a long-term memory. Nuclear receptors compose a class of transcription factors that regulate diverse biological processes, and several nuclear receptors have been implicated in memory formation. Here, we examined the potential contribution of nuclear receptors to memory consolidation by measuring the expression of all 49 murine nuclear receptors after learning. We identified 13 nuclear receptors with increased expression after learning, including all 3 members of the Nr4a subfamily. These CREB-regulated Nr4a genes encode ligand-independent "orphan" nuclear receptors. We found that blocking NR4A activity in memory-supporting brain regions impaired long-term memory but did not impact short-term memory in mice. Further, expression of Nr4a genes increased following the memory-enhancing effects of histone deacetylase (HDAC) inhibitors. Blocking NR4A signaling interfered with the ability of HDAC inhibitors to enhance memory. These results demonstrate that the Nr4a gene family contributes to memory formation and is a promising target for improving cognitive function.

Elevated intraocular pressure-induced interlamellar stromal keratitis occurring 9 years after laser in situ keratomileusis.

Elevated intraocular pressure-induced interlamellar stromal keratitis (PISK) is an entity of interface haze usually occurring weeks to months after laser in situ keratomileusis (LASIK) that is associated with elevated intraocular pressures and worsening with steroid treatment. There is evidence that this interface haze is the result of abnormal fluid dynamics that occur in the cornea after LASIK. We present a case of pressure-induced interlamellar stromal keratitis occurring 9 years after LASIK in the setting of anterior uveitis. This case emphasizes the importance of considering such diagnoses as pressure-induced interlamellar stromal keratitis in the differential diagnosis when presented with a patient with corneal haze and a history of LASIK.

A significant drug-drug interaction detected through corneal examination: resolution of cornea verticillata while using amiodarone.

PURPOSE: To describe a patient with resolution of cornea verticillata while still using amiodarone as a result of a drug interaction lowering serum levels of amiodarone. METHODS: An 83-year-old retired physician with long-standing cornea verticillata was noted to have complete resolution of cornea verticillata on a routine follow-up eye examination. The patient reported complete compliance with using amiodarone daily, with no recent changes in dosage or formulation. Despite this, he reported a recent increase in the frequency of palpitations. He had recently started rifampin for treatment of tuberculosis. RESULTS: Serum amiodarone and desethylamiodarone levels were obtained and found to be below therapeutic range. After rifampin was discontinued, serum amiodarone and desethylamiodarone levels increased to a therapeutic range and cornea verticillata returned after 4 months. CONCLUSIONS: In patients currently using amiodarone, clearing of cornea verticillata should alert the ophthalmologists to the possibility of decreased serum amiodarone levels.

Pupillary block glaucoma associated with a secondary piggyback intraocular lens.

A 53-year-old woman developed pupillary block glaucoma associated with iris capture of a piggyback intraocular lens (IOL) that was treated with laser peripheral iridotomy. The piggyback IOL was repositioned by dilating the iris pharmacologically and reclining the patient. The IOL maintained its proper position behind the iris with the use of low-concentration pilocarpine eyedrops. Pupillary block glaucoma can occur as a complication of secondary piggyback IOL implantation.

Conjunctival Kaposi's sarcoma in a nonimmunocompromised patient.

CASE REPORT: We report a case of conjunctival Kaposi's sarcoma (KS) in a nonimmunocompromised patient. The resected tumour recurred locally. No additional lesion was seen 20 months after the second surgery. COMMENTS: Before onset of AIDS, few reports described primary conjunctival KS, although it has been described in other immunocompromised disease stages, i.e. systemic KS.