Fungal keratitis caused by Coniochaeta mutabilis-A case report.

We present a rare case of recalcitrant fungal keratitis caused by Coniochaeta mutabilis, successfully managed with a course of oral, topical, intrastromal, and intracameral antifungals. A 57-year-old male on their fourth week of treatment for presumed left herpes simplex keratitis presented to clinic with severe left-sided foreign body sensation after gardening in his yard. On examination, a white corneal plaque was observed at 8 o'clock, shown to be a dense collection of fungal hyphae on confocal microscopy. Corneal cultures revealed yeast-like cells, initially identified as Kabatiella zeae by matching 100% identity with K. zeae strains CBS 767.71 and CBS 265.32 in BLASTn search using the internal transcribed spacer (ITS) sequence. Treated for over four months with topical amphotericin B and oral voriconazole without improvement, recourse to intrastromal and intracameral amphotericin B injections, coupled with the application of cyanoacrylate glue to the lesion and a bandage contact lens, led to eventual resolution. The patient subsequently underwent cataract surgery, achieving a BCVA of 20/20 in the eye. Surprisingly, upon further sequence analyses of combined ITS and large subunit ribosomal ribonucleic acid (LSU) and investigation of the K. zeae German strain CBS 767.71, the organism was revealed to be Coniochaeta mutabilis (formerly Lecythospora mutabilis). This means that the correct name for CBS 767.71 and CBS 265.32 is C. mutabilis and should be corrected in the GenBank record to avoid misleading identification in the future. This case also underscores the urgent unmet need for improved molecular diagnostic modalities in the care of corneal infections.

Incidence and risk factors for glaucoma development and progression after corneal transplantation.

OBJECTIVE: To assess the cumulative incidence and risk factors for glaucoma development and progression within 1-2 years following corneal transplant surgery. DESIGN: Retrospective cohort study. METHODS: Patients undergoing penetrating keratoplasty (PK), deep anterior lamellar keratoplasty (DALK), Descemet stripping endothelial keratoplasty (DSEK), Descemet membrane endothelial keratoplasty (DMEK), Boston keratoprosthesis type I (KPro) implantation, or endothelial keratoplasty (DSEK or DMEK) under previous PK (EK under previous PK) at one academic institution with at least 1 year of follow-up were included. Primary outcome measures were cumulative incidence of glaucoma development and progression after corneal transplant, in patients without and with preoperative glaucoma, respectively. Risk factors for glaucoma development and progression were also assessed. RESULTS: Four hundred and thirty-one eyes of 431 patients undergoing PK (113), DALK (17), DSEK (71), DMEK (168), KPro (35) and EK under previous PK (27) with a mean follow-up of 22.9 months were analyzed. The 1-year cumulative incidence for glaucoma development and progression was 28.0% and 17.8% in patients without and with preoperative glaucoma, respectively. In a Cox proportional hazards analysis, DSEK surgery, KPro implantation, average intraocular pressure (IOP) through follow-up and postoperative IOP spikes of ≥30 mmHg were each independently associated with glaucoma development or progression (p < 0.04 for all). CONCLUSIONS: A significant proportion of patients developed glaucoma or exhibited glaucoma progression within 1 year after corneal transplantation. Patient selection for DSEK may partly explain the higher risk for glaucoma in these patients. Postoperative IOP spikes should be minimized and may indicate the need for co-management with a glaucoma specialist.

COVID-19 and the Unfinished Agenda of VISION 2020.

PURPOSE: To critically evaluate the potential impact of the coronavirus disease (COVID-19) pandemic on global ophthalmology and VISION 2020. DESIGN: Perspective supplemented with epidemiologic insights from available online databases. METHODS: We extracted data from the Global Vision Database (2017) and Global Burden of Disease Study (2017) to highlight temporal trends in global blindness since 1990, and provide a narrative overview of how COVID-19 may derail progress toward the goals of VISION 2020. RESULTS: Over 2 decades of VISION 2020 advocacy and program implementation have culminated in a universal reduction of combined age-standardized prevalence of moderate-to-severe vision impairment (MSVI) across all world regions since 1990. Between 1990 and 2017, low-income countries observed large reductions in the age-standardized prevalence per 100,000 persons of vitamin A deficiency (25,155 to 19,187), undercorrected refractive disorders (2,286 to 2,040), cataract (1,846 to 1,690), onchocerciasis (5,577 to 2,871), trachoma (506 to 159), and leprosy (36 to 26). Despite these reductions, crude projections suggest that more than 700 million persons will experience MSVI or blindness by 2050, principally owing to our growing and ageing global population. CONCLUSIONS: Despite the many resounding successes of VISION 2020, the burden of global blindness and vision impairment is set to reach historic levels in the coming years. The impact of COVID-19, while yet to be fully determined, now threatens the hard-fought gains of global ophthalmology. The postpandemic years will require renewed effort and focus on vision advocacy and expanding eye care services worldwide.

Mystery eye: Human adenovirus and the enigma of epidemic keratoconjunctivitis.

Known to occur in widespread outbreaks, epidemic keratoconjunctivitis (EKC) is a severe ocular surface infection with a strong historical association with human adenovirus (HAdV). While the conjunctival manifestations can vary from mild follicular conjunctivitis to hyper-acute, exudative conjunctivitis with formation of conjunctival membranes, EKC is distinct as the only form of adenovirus conjunctivitis in which the cornea is also involved, likely due to the specific corneal epithelial tropism of its causative viral agents. The initial development of a punctate or geographic epithelial keratitis may herald the later formation of stromal keratitis, and manifest as subepithelial infiltrates which often persist or recur for months to years after the acute infection has resolved. The chronic keratitis in EKC is associated with foreign body sensation, photophobia, glare, and reduced vision. However, over a century since the first clinical descriptions of EKC, and over 60 years since the first causative agent, human adenovirus type 8, was identified, our understanding of this disorder remains limited. This is underscored by a current lack of effective diagnostic tools and treatments. In part, stasis in our knowledge base has been encouraged by the continued acceptance, and indeed propagation of, inaccurate paradigms pertaining to disease etiology and pathogenesis, particularly with regard to mechanisms of innate and adaptive immunity within the cornea. Owing to its often persistent and medically refractory visual sequelae, reconsideration of key aspects of EKC disease biology is warranted to identify new treatment targets to curb its worldwide socioeconomic burden.

Validation of a Comprehensive Clinical Algorithm for the Assessment and Treatment of Microbial Keratitis.

PURPOSE: To validate a comprehensive clinical algorithm for the assessment and treatment of microbial keratitis (MK). DESIGN: Retrospective cohort study. METHODS: The "1, 2, 3 Rule" for the initial management of MK was conceived by Vital and associates in 2007 to inform the decision as to when to perform corneal cultures. The rule is invoked when any 1 of 3 clinical parameters is met: ≥1+ anterior chamber cells, ≥2 mm infiltrate, or infiltrate ≤3 mm distance from the corneal center. When the rule is met, we added the mandatory use of fortified topical antibiotics after cultures are obtained. We compared outcomes of cases presenting to Massachusetts Eye and Ear 2 years before (Group I, n = 665) and after (Group II, n = 767) algorithm implementation. The primary composite outcome was a vision-threatening complication, such as corneal perforation. RESULTS: At a median follow-up of 67.0 and 60.0 days, respectively, 172 patients experienced a vision-threatening complication (Group I, 12.9% vs Group II, 11.2%, P = .51). While the algorithm codified conventional management practice at either end of disease severity, the effect of algorithm-augmented care was best appreciated in patients with lesions satisfying only 1 criterion. In this group, there was an increase in the proportion of patients undergoing culture at presentation (54.6% vs 67.7%, P = .006), fortified antibiotic prescription (29.7% vs 53.9%, P < .001), and reduction in vision-threatening complications (9.7% vs 1.8%, P = .001). The proportion of patients who were not cultured at presentation but later required culturing decreased (13.4% vs 5.1%, P = .001), as did patients who did not meet any criteria but were nonetheless cultured (23.9% vs 8.5%, P < .001). Multiple logistic regression showed that all algorithm parameters were independently associated with outcome: ≥1+ anterior chamber cells (odds ratio [OR] 1.66, 95% confidence interval 1.09-2.52); ≥2 mm infiltrate (OR 4.74, 2.68-8.40); and ≤3 mm from corneal center (OR 2.82, 1.85-4.31), confirmed with comparison to a bootstrapped sample (n = 10,000). CONCLUSIONS: The implementation of this algorithm reduced vision-threatening complications for patients with lesions satisfying only 1 criterion, arguably the most difficult patients in whom to judge disease severity. Implementation also led to a decrease in patients receiving unnecessary care.

Synchronous liver resection with cytoreductive surgery for the treatment of liver and peritoneal metastases from colon cancer: results from an Australian centre.

BACKGROUND: Treatment of peritoneal metastases (PM) and liver metastases (LM) from colon cancer remains controversial. LM has been viewed as exclusion criterion for cytoreductive surgery (CRS) on the basis that such spread represents systemic disease. CRS and intraperitoneal chemotherapy (IPC) has gained increasing recognition as a treatment modality for selected patients with colon cancer and PM. This study analyses results of CRS and IPC for colon cancer and synchronous resection for treatment of LM and PM. METHODS: Seventy-eight patients with PM/LM colon cancer were analysed. Forty-two patients with PM were treated for disease limited to the peritoneum (A), and 36 patients received treatment for both PM and LM (B). Overall survival (OS), disease-free survival (DFS), morbidity, mortality and recurrence were compared. RESULTS: Median OS and DFS was 32.8 and 13.5 months. The median OS for A and B were 45.5 and 24.4 months respectively. Within B patients, 18 had a peritoneal carcinomatosis index (PCI) >7 and >3 LM and median survival of 21.8 months compared with 18 patients with PCI ≤7 and LM ≤3 with median survival of 38.4 months. Median DFS for A and B were 17.7 and 8.5 months respectively. Twenty-seven in total experienced major complications following surgery. Sixty-one patients recurred. Of A, 71.4% recurred compared with B at 86.1%. CONCLUSION: While our study is limited, it has demonstrated encouraging evidence that long-term survival outcomes can be achieved in this small but significant number of patients treated by CRS/IPC and additional synchronous liver resection with no significant increase in morbidity when compared with CRS/IPC alone.

The importance of gender in patients with peritoneal metastases of appendiceal origin treated by cytoreduction and intraperitoneal chemotherapy: an analysis of 257 consecutive patients from an Australian centre.

BACKGROUND AND OBJECTIVES: In the setting of colorectal cancer, female gender has been associated with superior long-term outcomes. Our aim is to investigate the gender differences for metastatic epithelial neoplasms of the appendix treated by cytoreductive surgery (CS) and intraperitoneal chemotherapy (IPC). METHODS: The survival outcomes of patients treated with CS/IPC from 1996 to 2013 at St. George Hospital, Sydney, Australia, for peritoneal metastases of appendiceal origin were retrospectively analysed. RESULTS: Two hundred and fifty-seven consecutive patients were followed for a median of 35.3 months. Baseline characteristics between genders were comparable, including age (p = 0.13) and peritoneal cancer index (p = 0.94). Median overall survival (OS) and progression-free survival (PFS) was not reached (NR) and 44.4 months, with a 3-, 5- and 10-year survival of 82, 74 and 64 %. OS and PFS for females was NR and 50.7 months, compared to NR (p = 0.007) and 31.5 months for males (p = 0.07). Three-, 5- and 10-year survival rates for females were 88, 84 and 72 % compared to 74, 61 and 53 % for males. CONCLUSION: Observed gender differences for neoplasms of the appendix may direct future research in gender-specific tumour markers and the development of adjuvant therapies to improve patient outcomes.

Peritoneal metastases of lower gastrointestinal tract origin: a comparative study of patient outcomes following cytoreduction and intraperitoneal chemotherapy.

BACKGROUND: Cytoreductive surgery (CS) combined with intraperitoneal chemotherapy (IPC) is a multimodal approach to the treatment of peritoneal metastases (PM) of lower gastrointestinal origin. This study examines patient outcomes and critically evaluates its patterns of recurrences relative to the site of metastatic origin. METHODS: Patients treated with CS/IPC from 2000 to 2012 where PM arose from a primary tumour of the appendix, colon and rectum were identified from a prospective database for retrospective evaluation. The primary end points were survival (overall and disease-free), and secondary end points include patterns of recurrence and prognostic factors associated with overall outcomes. RESULTS: Two hundred and eleven patients were followed up for a median of 23.3 months (range 1-156). Overall median survival was 46.8 months, and the 1-, 3-, 5-year survival rates were 87, 56 and 42 %, respectively. The 5-year survival of patients with appendiceal, colonic and rectal PM was 55, 33 and 20 %, respectively. Tumour origin was the only independent prognostic factor associated with overall survival (p = 0.03). Recurrences were more common in patients of colorectal origin over appendiceal origin (p < 0.001) and were more likely to be of a systemic nature (p = 0.05). CONCLUSION: CS/IPC provides an option for improved survival in patients with PM of lower gastrointestinal origin and appears to be most promising in patients with disease of appendiceal origin.

Peritoneal metastases of lower gastrointestinal tract origin:a comparative study of patient outcomes following cytoreduction and intraperitoneal chemotherapy.

BACKGROUND: Cytoreductive surgery (CS) combined with intraperitoneal chemotherapy (IPC) is a multimodal approach to the treatment of peritoneal metastases (PM) of lower gastrointestinal origin. This study examines patient outcomes and critically evaluates its patterns of recurrences relative to the site of metastatic origin. METHODS: Patients treated with CS/IPC from 2000 to 2012 where PM arose from a primary tumour of the appendix, colon and rectum were identified from a prospective database for retrospective evaluation. The primary endpoints were survival (overall and disease-free), and secondary end points include patterns of recurrence and prognostic factors associated with overall outcomes. RESULTS: Two hundred and eleven patients were followed up for a median of 23.3 months (range 1­156). Overall median survival was 46.8 months, and the 1-, 3-, 5-year survival rates were 87, 56 and 42 %, respectively. The 5-year survival of patients with appendiceal, colonic and rectal PM was 55, 33 and 20 %, respectively. Tumour origin was the only independent prognostic factor associated with overall survival (p = 0.03). Recurrences were more common in patients of colorectal origin over appendiceal origin (p\0.001) and were more likely to be of a systemic nature (p = 0.05). CONCLUSION: CS/IPC provides an option for improved survival in patients with PM of lower gastrointestinal origin and appears to be most promising in patients with disease of appendiceal origin.

Cure for peritoneal metastases? An evidence-based review.

There is now a considerable body of published evidence supporting the use of a multimodal approach consisting of cytoreductive surgery (CS) and heated intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal metastases (PM) arising from selected gastrointestinal tract malignancies. In the absence of systemic metastases, it is thought that disease confined to the peritoneum may be eradicated through optimum cytoreduction. This review critically evaluates the current body of published evidence for the use of CS/HIPEC in the treatment of advanced colorectal, appendiceal and gastric cancer. Although its role remains less defined in patients with gastric PM, current evidence provides a compelling argument for its use in PM of colorectal and appendiceal origin. With a low mortality and acceptable morbidity rate, CS/HIPEC may offer hope of long-term survival and cure in a defined group of patients with this disease.