Fungal diseases kill more than 1.5 million and affect over a billion people. However, they are still a neglected topic by public health authorities even though most deaths from fungal diseases are avoidable. Serious fungal infections occur as a consequence of other health problems including asthma, AIDS, cancer, organ transplantation and corticosteroid therapies. Early accurate diagnosis allows prompt antifungal therapy; however this is often delayed or unavailable leading to death, serious chronic illness or blindness. Recent global estimates have found 3,000,000 cases of chronic pulmonary aspergillosis, ~223,100 cases of cryptococcal meningitis complicating HIV/AIDS, ~700,000 cases of invasive candidiasis, ~500,000 cases of Pneumocystis jirovecii pneumonia, ~250,000 cases of invasive aspergillosis, ~100,000 cases of disseminated histoplasmosis, over 10,000,000 cases of fungal asthma and ~1,000,000 cases of fungal keratitis occur annually. Since 2013, the Leading International Fungal Education (LIFE) portal has facilitated the estimation of the burden of serious fungal infections country by country for over 5.7 billion people (>80% of the world’s population). These studies have shown differences in the global burden between countries, within regions of the same country and between at risk populations. Here we interrogate the accuracy of these fungal infection burden estimates in the 43 published papers within the LIFE initiative.

https://www.mdpi.com/2309-608X/3/4/57/pdf/1

Global and Multi-National Prevalence of Fungal Diseases—Estimate Precision

Fungal keratitis is a severe corneal infection that often results in blindness and eye loss. The disease is most prevalent in tropical and subtropical climates, and infected individuals are frequently young agricultural workers of low socioeconomic status. Early diagnosis and treatment can preserve vision. Here, we discuss the fungal keratitis diagnostic literature and estimate the global burden through a complete systematic literature review from January, 1946 to July, 2019. An adapted GRADE score was used to evaluate incidence papers-116 studies provided the incidence of fungal keratitis as a proportion of microbial keratitis and 18 provided the incidence in a defined population. We calculated a minimum annual incidence estimate of 1 051 787 cases (736 251-1 367 323), with the highest rates in Asia and Africa. If all culture-negative cases are assumed to be fungal, the annual incidence would be 1 480 916 cases (1 036 641-1 925 191). In three case series, 8-11% of patients had to have the eye removed, which represents an annual loss of 84 143-115 697 eyes. As fungal keratitis probably affects over a million people annually, an inexpensive, simple diagnostic method and affordable treatment are needed in every country.

The global incidence and diagnosis of fungal keratitis.

To describe the clinical features, management and outcomes in patients with fungal keratitis at the Sydney Eye Hospital, Australia, over a 9-year period to guide appropriate initial therapy. A retrospective case review was conducted. Patients diagnosed with fungal keratitis from 1 January 2009 to 31 December 2017 were identified from hospital coding and pathology databases. Data were extracted from the medical records. A total of 55 episodes from 51 patients were included. Mean age was 60 ± 20 years (range: 19-91 years), and 33 were male. The fungal species was not identified in two patients. Predisposing factors included ocular surface disease in 17 eyes (32%); corneal disease, 15 (28%); corneal trauma, 12 (23%); and contact lens wear, 13 (24.5%). Fusarium spp. (15, 27%) and Candida parapsilosis (10, 18%) were the most common isolates. The median visual acuity at presentation was 1.3 logMAR (range: 0 to 3) and after treatment 0.7 logMAR (range: -0.02 to 3) (P = .008). Despite medical therapy, most commonly with natamycin and topical and oral voriconazole, surgical intervention was required in 21 eyes (40%); including antifungal injections in 9 (16%); corneal transplantation, 16 (30%); evisceration, 2 (4%); and enucleation, 1 (2%). A poor visual outcome was recorded in 27 of 43 (63%) patients. Fungal keratitis remains a cause of significant ocular morbidity; the majority of patients face a poor outcome despite intense medical and at times surgical treatment. In our setting, fungal keratitis was more commonly associated with corneal or ocular surface disease.

The clinical and microbiological features and outcomes of fungal keratitis over 9 years in Sydney, Australia.

Pigmentary glaucoma (PG) is a common glaucoma subtype that results from release of pigment from the iris, called pigment dispersion syndrome (PDS), and its deposition throughout the anterior chamber of the eye. Although PG has a substantial heritable component, no causative genes have yet been identified. We used whole exome sequencing of two independent pedigrees to identify two premelanosome protein (PMEL) variants associated with heritable PDS/PG. PMEL encodes a key component of the melanosome, the organelle essential for melanin synthesis, storage and transport. Targeted screening of PMEL in three independent cohorts (n = 394) identified seven additional PDS/PG-associated non-synonymous variants. Five of the nine variants exhibited defective processing of the PMEL protein. In addition, analysis of PDS/PG-associated PMEL variants expressed in HeLa cells revealed structural changes to pseudomelanosomes indicating altered amyloid fibril formation in five of the nine variants. Introduction of 11-base pair deletions to the homologous pmela in zebrafish by the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 method caused profound pigmentation defects and enlarged anterior segments in the eye, further supporting PMEL's role in ocular pigmentation and function. Taken together, these data support a model in which missense PMEL variants represent dominant negative mutations that impair the ability of PMEL to form functional amyloid fibrils. While PMEL mutations have previously been shown to cause pigmentation and ocular defects in animals, this research is the first report of mutations in PMEL causing human disease.

Non-Synonymous variants in premelanosome protein (PMEL) cause ocular pigment dispersion and pigmentary glaucoma

https://www.pure.ed.ac.uk/ws/files/77753169/2018_ABB_accepted_manuscript.pdf

Fluorescent peptides for imaging of fungal cells

Objective To study the post-treatment visual outcome of fungal keratitis. Methods This prospective study was carried out at Chandka Medical College and Hospital, Larkana, Pakistan, from March 2005 to March 2016. Patients with clinical features of fungal keratitis, with positive corneal scrapings for fungi, and those who followed up for a minimum period of three months after recovery from infection were included.Other causes of infectious keratitis were excluded. The clinical diagnosis of fungal keratitis was based on risk factor identification and characteristic non-specific and specific corneal features. Treatment included antifungal preparations, topical and if necessary systemic, in addition to symptomatic measures. SPSS 20 was used for data analysis. Results Of the 1,130 patients, 750(66.37%) were males and 380(33.63%) were females. The overall mean age was 39.44±12.46 years (range:16-74 years). After the completion of treatment, 590(52.21%) of the eyes just retained visual acuity of not more than counting fingers and 126(11.15%) patients lost their globe. Patients with remaining corneal opacity needed keratoplasty. Conclusions Most of the eyes just retained visual acuity of counting fingers while some patients lost their globe.

Visual outcome in patients of keratomycosis, at a tertiary care centre in Larkana, Pakistan.

Background: Pigment Dispersion Syndrome (PDS) is an autosomal dominant disorder of white males between 20 to 40 years of age characterized by deposition of pigment on the lens, zonules of lens, trabecular meshwork and corneal endothelium (Krukenberg’s spindle) in addition to radial, spoke like transillumination defects in the mid peripheral iris. This study was conducted to determine the frequency of occurrence of Pigmentary Glaucoma in patients with Pigment Dispersion Syndrome (PDS). Methods: This longitudinal follow up study included patients presenting with Krukenberg’s spindle on the endothelial side of cornea and pigmentation of angle of anterior chamber seen on slit lamp examination and gonioscopy. Results: Seventy-two cases of PDS were included in the study, amongst them 63 (87.50%) were males. Mean age was 35.00±6.54 years (range 24–46 years). Forty-seven (65.28%) patients had an IOP in the range of 10–14 mmHg, 22 (30.56%) patients had an IOP in the range of 15–18 mmHg and 3 (4.17%) patients developed an IOP of greater than 19 mmHg. Fundoscopy showed myopic degeneration in 49 (68.06%) patients and optic disc cupping in 3 (4.17%) patients. Four (5.56%) patients had refractive error between +1D to +3D, 9 (12.50%) patients had refractive error between -1D to -4D, 21 (29.17%) patients had refractive error between -5 D to -8 D and 38 (52.78%) patients had refractive error between -9 D to -12 D.  Our study showed that one patient having PDS developed glaucoma at 5 years of follow up and three patients developed glaucoma at 14 years of follow up. Conclusion: On the basis of this study we conclude that early onset primary open angle glaucoma associated with PDS or Juvenile glaucoma associated with PDS might have been mistaken as Pigmentary Glaucoma in Pakistani patients and a distinct entity in the form of Pigmentary Glaucoma may be non-existent. Keywords: Pigment dispersion syndrome; Pigmentary glaucoma; Open angle glaucoma; Pigment epithelium; Trabecular meshwork; Trans-illumination

Determination Of Association Of Pigmentary Glaucoma With Pigment Dispersion Syndrome.

Material and Methods: This prospective case series study was conducted from September 1999 to September 2014 at ophthalmology department Chandka medical college and Syed eye clinic, Larkana, Pakistan. Patients identified clinically as cases of hypovitaminosis A on the basis of presence of “Imtiaz’s sign” were included in the study. Patients with Retinitis pigmentosa, glaucoma, chronic liver disease and malabsorption syndrome were excluded from the study. Imtiaz's sign of vitamin A deficiency and nyctalopia were noted and relevant laboratory investigations available were also done on selected patients. Patients were given therapeutic doses of vitamin A and improvement was observed to see resolution of Imtiaz’s sign of vitamin A deficiency and remission of nyctalopia.

Assessment of "Imtiaz's Sign" for Early Detection of Hypovitaminosis A

The objective of this study was to determine the pattern of traumatic lens dislocations presenting at our institute. This may help develop the preventive strategies. The number of cases of traumatic lens dislocations, presented at the Department of Ophthalmology, Chandka Medical College, Larkana, Pakistan, from January 2002 to June 2015, were 59 including 61.02% (n=36) males and 38.98% (n=23) females. Cause of trauma was wood or plant impalement in 35.6% (n=21) cases, cracker blast in 13.55% (n=8) cases, fall on ground in 11.86% (n=7) cases, penetrating injuries with needle, scissors or knife in 10.16% (n=6) cases, road traffic accidents in 10.16% (n=6) cases, sports injuries (cricket ball and gulle danda) in 8.47% (n=5) cases, firearm injuries in 5.1% (n=3) cases, and fist hitting in 5.1% (n=3) cases. Lens was dislocated posteriorly in 33.90% (n=20) cases, anteriorly in 25.42% (n=15) cases, inferiorly in 11.86% (n=7) cases, medially in 10.17% (n=6) cases, laterally in 10.17% (n=6) cases, superiorly in 6.78% (n=4) cases, and a single (1.69%) case of lenticele was seen.

Types of Traumatic Lens Dislocations at Larkana.

Objectives: The objective of this study is to compare the surgical outcome between modified trabeculotomy v/s combined modified trebeculotomy & trebeculectomy in primary congenital glaucoma. Study Design: Interventional case series. Setting: Paediatric Ophthalmology Department, Chandka Medical College. Period: June 2016 to June 2017. Method: This is a comparative study done to compare the outcomes of trabeculectomy and combined trabeculotomy and trabeculectomy. For comparison a prospective interventional study conducted in paediatric ophthalmology, Chandka Medical College during the duration of August 2014 to August 2016 was chosen. After examination by slit lamp and under anaesthesia, combined modified trabeculotomy and trabeculectomy was performed. Results: A total of 45 eyes of 29 patients with primary congenital glaucoma underwent modified trabeculotomy, 15 (51.72%) were males and 14 (48.28%) were females. Mean age of patients was 2.29 ± 3.70 years. On the other hand, combined modified trabeculotomy and trabeculectomy was performed in 22 eyes of 17 patients out of which 08 (47.06%) were males and 09 (52.94%) were females. Mean age ± standard deviation was 3.37 ± 4.40 years. Statistically significant reduction in IOP, corneal diameter and axial length were found. Conclusion: Combined trabeculotomy-trabeculectomy has better outcomes than trabeculotomy alone. It requires greater surgical expertise and time. Higher success rates are reported in previous studies due to dual outflow of aqueous humour.

/pdf/primary-congenital-glaucoma-4f97fzona0.pdf

Safdar Ali Abbasi

Papers

Visual outcome in patients of keratomycosis, at a tertiary care centre in Larkana, Pakistan.

Determination Of Association Of Pigmentary Glaucoma With Pigment Dispersion Syndrome.

Assessment of "Imtiaz's Sign" for Early Detection of Hypovitaminosis A

Types of Traumatic Lens Dislocations at Larkana.

Primary congenital glaucoma