A chromosome 4 trisomy contributes to increased fluconazole resistance in a clinical isolate of Candida albicans.

Candida albicans is an important opportunistic fungal pathogen capable of causing both mucosal and disseminated disease. Infections are often treated with fluconazole, a front-line antifungal drug that targets the biosynthesis of ergosterol, a major component of the fungal cell membrane. Resistance to fluconazole can arise through a variety of mechanisms, including gain-of-function mutations, loss of heterozygosity events and aneuploidy. The clinical isolate P60002 was found to be highly resistant to azole-class drugs, yet lacked mutations or chromosomal rearrangements known to be associated with azole resistance. Transcription profiling suggested that increased expression of two putative drug efflux pumps, CDR11 and QDR1, might confer azole resistance. However, ectopic expression of the P60002 alleles of these genes in a drug-susceptible strain did not increase fluconazole resistance. We next examined whether the presence of three copies of chromosome 4 (Chr4) or chromosome 6 (Chr6) contributed to azole resistance in P60002. We established that Chr4 trisomy contributes significantly to fluconazole resistance, whereas Chr6 trisomy has no discernible effect on resistance. In contrast, a Chr4 trisomy did not increase fluconazole resistance when present in the standard SC5314 strain background. These results establish a link between Chr4 trisomy and elevated fluconazole resistance, and demonstrate the impact of genetic background on drug resistance phenotypes in C. albicans.

Combinative approach of transzonular triamcinolone-moxifloxacin and perioperative drops to minimize postoperative complications of cataract surgery.

AIM: To investigate the effectiveness of combination therapy with transzonular triamcinolone-moxifloxacin and conventional perioperative drops in reducing postoperative complications of cataract surgery. METHODS: Electronic medical records of cataract surgery patients (single surgeon) were reviewed from January 2018 to September 2021. The rate of postoperative complications including prolonged and/or recurrent postoperative inflammation, endophthalmitis, cystoid macular edema (CME), and intraocular pressure (IOP) was compared between the patients receiving combinative therapy and patients receiving drops only. RESULTS: Totally 596 patients and 1057 eyes (Combinative-Therapy group 493 and Drop-Only group 564) were included in this study. Using combination therapy reduced the relative risk of postoperative inflammation by 26.9% (16.6% Combinative-Therapy vs 22.7% Drop-Only, P=0.013). The incidence of endophthalmitis was 0 in Combinative-Therapy group vs 0.5% in Drop-Only group (relative risk reduction 100%), although not statistically significant (P=0.10). The incidence of severe IOP spikes was not significantly different between Combinative-Therapy (2.4%) and Drop-Only (1.6%) groups (P=0.33). The relative risk of postoperative CME was 51.4% less in three months follow up visit in Combinative-Therapy group, although not statistically significant (P=0.07). The visual outcome 1-month postop. (best corrected visual acuity) was significantly better in Combinative-Therapy (logMAR 0.10) compared to Drop-Only (logMAR 0.14) groups (P=0.02) while the baseline visual acuity was not significantly different. CONCLUSION: The combinative approach of transzonular triamcinolone-moxifloxacin plus perioperative eyedrops is an effective method to minimize postoperative inflammation, with better visual outcomes. It could potentially reduce the risk of postoperative endophthalmitis and CME (near-significant P-values; larger studies could analyze better considering low incidence).

Long-term outcomes of glued (sutureless) amniotic membrane transplantation in acute Stevens-Johnson syndrome/toxic epidermal necrolysis: a comparative study.

PURPOSE: To compare the effectiveness and efficiency of a glued (sutureless) technique for amniotic membrane transplantation (AMT) with a traditional sutured one in the setting of acute Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). METHODS: This retrospective cohort study evaluated all patients diagnosed with SJS/TEN between 2008 and 2020 within our hospital network who received AMT in the acute phase according to our protocol and had at least one ophthalmic follow-up in the chronic phase. Primary outcomes included best-corrected visual acuity (BCVA) at the most recent visit, presence of a severe ocular complication (SOC) via predefined criteria, time to procedure and duration of procedure. Random effects model analysis was used to evaluate the impact of potential covariates on outcome measures. RESULTS: A total of 23 patients (45 eyes) were included: 14 patients (27 eyes) in the AMT suture group and 9 patients (18 eyes) in the AMT glue group. There was no difference between the two groups in BCVA at the most recent visit (p=0.5112) or development of a SOC (p=1.000). The glue method was shorter in duration than the suture method (p<0.001). Random effects model additionally indicated that there was no difference in BCVA at most recent follow-up between patients who had received glued versus sutured AMT (p=0.1460). CONCLUSIONS: Our glued technique for AMT is as effective as our sutured technique in stabilising the ocular surface and mitigating chronic ocular complications in SJS/TEN. The glued technique is also shorter in duration and performed more expediently than the sutured technique.

A Comparative Study of Ocular Surface Disease in Childhood Glaucoma.

PURPOSE: To evaluate ocular surface disease (OSD) in patients with childhood glaucoma (CG). METHODS: A multicenter, comparative, cross-sectional study of 41 eyes of 27 patients with CG and 42 eyes of 42 healthy age- and sex-matched controls was conducted between 2021 and 2022. Developmentally delayed children and those having a coexisting systemic illness that might affect the ocular surface were not enrolled. Data collected included glaucoma type, glaucoma medications and surgeries, anterior segment examination, symptom frequency and severity, and tear break-up time (TBUT). Dry eye disease (DED) symptoms were evaluated using an Arabic-language SPEED questionnaire. RESULTS: The average number of glaucoma medications and surgeries among the 27 patients with CG was 1.17 and 1.4, respectively. TBUT was shorter in patients with CG compared with controls and even shorter when glaucoma medication usage was accounted for. Punctate epithelial erosions were more prevalent in patients with CG and of a higher grade. The severity of all DED parameters, and the prevalence of all DED parameters except for eye fatigue, were greater in patients with CG on the day of questionnaire intake. In addition, each additional glaucoma drop was associated with worse TBUT and ocular surface dryness. All analyses mentioned above were statistically significant (P < 0.05). CONCLUSIONS: In this first study to comprehensively evaluate OSD in patients with CG, a significantly greater incidence of OSD signs and symptoms was found in patients with CG compared with a healthy population. Additional study by CG subtype is needed.

Regression of treatment-resistant gyrate atrophy-associated intraretinal cystic spaces using long-term diet restriction: A case report.

PURPOSE: Gyrate atrophy of the choroid and retina (GA) is a rare genetic ophthalmologic condition which primarily manifests in childhood. It is characterized by hyperornithinemia and progressive chorioretinal atrophy. Patients may develop macular intraretinal cystic spaces (ICS) for which various treatment modalities have been reported. We report a patient who failed to demonstrate visual or anatomic improvement following multiple treatments for GA-associated ICS but showed improvement following prolonged dietary modification and vitamin supplementation. CASE DESCRIPTION: A 6-year-old male patient presented with previously undiagnosed GA associated with ICS. He received 6 consecutive monthly intravitreal bevacizumab injections as well as topical nepafenac and dorzolamide for treatment of ICS without significant change detected by optical coherence tomography (OCT) following treatment. He was also maintained on an arginine restricted diet with vitamin B6 supplementation. Over the course of the ensuing year, the patient was lost to follow-up due to the coronavirus disease 2019 pandemic. When he returned, his vision was stable, and OCT showed regression of the ICS. His mother reported that he had continued only on dietary restriction and vitamin B6 supplementation with no other medications or interventions. Plasma ornithine level measurement confirmed dietary compliance. Further follow-up showed continued stabilization of the condition. CONCLUSION: In addition to retarding progressive chorioretinal atrophy, prolonged dietary modifications may result in improvement of treatment-resistant GA-associated ICS. Parents' education on the value of dietary modifications for patients with GA is highly recommended.

A Systematic Review of Clinical Trials in Uveitis: Lessons Learned.

PURPOSE: Clinical trials in uveitis have led to the expansion of therapeutic options for the management of non-infectious uveitis. The purpose of this systematic review is to investigate why some clinical trials have yielded successful results and regulatory approval of new therapies, and some have not. METHODS: A systematic literature search of the Pubmed/MEDLINE database and clinicaltrials.gov was performed from 2006 to 2021, according to the PRISMA guidelines. Phase III clinical trials of systemic and local therapies in adults with non-infectious intermediate, posterior, and panuveitis were included. RESULTS: A total of 79 clinical trials were collected from ClinicalTrials.gov and PubMed/MEDLINE database search. Based on the inclusion and exclusion criteria, 14 clinical trials were included. CONCLUSION: This review summarizes the study design, outcome measures, and results of recent phase III trials in non-infectious uveitis, in the interest of understanding limitations and rethinking new methods of defining endpoints in clinical trial design.

Ocular involvement in Mycoplasma induced rash and mucositis: A systematic review of the literature.

Mycoplasma pneumoniae induced rash and mucositis (MIRM) is a relatively newly identified clinical entity which is characterized by mucocutaneous manifestations in the setting of Mycoplasma infection. Though a clinically distinct disease, MIRM exists on a diagnostic continuum with entities including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and the recently described reactive infectious mucocutaneous eruption (RIME). In this systematic review, we discuss published findings on the epidemiology, clinical manifestations, diagnosis, and management of MIRM, with an emphasis on ocular disease. Lastly, we discuss some of the most recent developments and challenges in characterizing MIRM with respect to the related diagnosis of RIME.

Ocular Complications Following Vaccination for COVID-19: A One-Year Retrospective.

Vaccination efforts as a mitigation strategy in the corona virus disease 2019 (COVID-19) pandemic are fully underway. A vital component of understanding the optimal clinical use of these vaccines is a thorough investigation of adverse events following vaccination. To date, some limited reports and reviews have discussed ocular adverse events following COVID-19 vaccination, but a systematic review detailing these reports with manifestations and clinical courses as well as proposed mechanisms has yet to be published. This comprehensive review one-year into vaccination efforts against COVID-19 is meant to furnish sound understanding for ophthalmologists and primary care physicians based on the existing body of clinical data. We discuss manifestations categorized into one of the following: eyelid, orbit, uveitis, retina, vascular, neuro-ophthalmology, ocular motility disorders, and other.

Down syndrome: a review of ocular manifestations.

Down syndrome is the most common genetically mediated intellectual disability. Although many physiologic and pathologic features of Down syndrome are discussed at length in the literature, the ocular manifestations of Down syndrome have seldom been discussed in a comprehensive fashion. Given that Down syndrome has ocular manifestations from the front to the back of the eye, it is important for physicians to become familiar with these manifestations, especially given the prevalence of Down syndrome. This review aims to discuss the varied ophthalmologic manifestations of Down syndrome - including strabismus, amblyopia, nystagmus, accommodation deficits, nasolacrimal duct obstruction, keratoconus, optic nerve pathology, neoplastic disease, and retinal pathology - to facilitate better care and visual outcomes in this important patient population.

Acute Uveitis following COVID-19 Vaccination.

PURPOSE: To describe a case of juvenile idiopathic arthritis (JIA)-associated anterior uveitis after receiving the Sinopharm COVID-19 vaccine. METHODS: A retrospective case report. RESULTS: An 18-year-old girl, with a history of antinuclear antibody positive oligoarticular JIA, presented with bilateral anterior uveitis 5 days after the second dose of the Sinopharm COVID-19 vaccine. Ocular examination revealed anterior uveitis with reduced visual acuity in both eyes. Anterior segment optical coherence tomography showed hyperreflective dots in the anterior chamber (AC) and fine endothelial granularities representing the circulating cells in the AC. Uveitis in both eyes resolved gradually after topical steroid treatment without recurrence. CONCLUSION: This report demonstrates a potential causal association of COVID-19 vaccine with anterior uveitis.

Fungal Endophthalmitis: A Comprehensive Review.

Endophthalmitis is a serious ophthalmologic condition involving purulent inflammation of the intraocular spaces. The underlying etiology of infectious endophthalmitis is typically bacterial or fungal. The mechanism of entry into the eye is either exogenous, involving seeding of an infectious source from outside the eye (e.g., trauma or surgical complications), or endogenous, involving transit of an infectious source to the eye via the bloodstream. The most common organism for fungal endophthalmitis is Candida albicans. The most common clinical manifestation of fungal endophthalmitis is vision loss, but other signs of inflammation and infection are frequently present. Fungal endophthalmitis is a clinical diagnosis, which can be supported by vitreous, aqueous, or blood cultures. Treatment involves systemic and intravitreal antifungal medications as well as possible pars plana vitrectomy. In this review, we examine these essential elements of understanding fungal endophthalmitis as a clinically relevant entity, which threatens patients' vision.