Parwez Hossain | University of Southampton (original) (raw)

Papers by Parwez Hossain

Research paper thumbnail of Peripheral Corneal Hydrops Secondary to Pellucid Marginal Degeneration Managed With a Manually Dissected Semicircular Endothelial Keratoplasty Lenticule

Cornea, Jan 16, 2018

To the Editor: We read with interest Tu’s1 report of using endothelial keratoplasty (EK) in a cas... more To the Editor: We read with interest Tu’s1 report of using endothelial keratoplasty (EK) in a case of nonresolving acute corneal hydrops secondary to keratoconus. EK has previously been used to treat other similar causes of corneal edema due to tears in Descemet’s membrane (DM), such as corneal hydrops in keratoglobus2 and late corneal decompensation secondary to obstetric forceps trauma.3 We report the case of a 42-year-old woman with peripheral corneal hydrops secondary to pellucid marginal degeneration (Fig. 1), successfully managed with EK. She had previously had a similar episode in her fellow eye, complicated by corneal perforation. After 6 weeks of nonresolution despite standard conservative treatment and air tamponade, the patient continued to be in severe pain and the threat of impending perforation led us to perform non-Descemet stripping EK with a manually dissected semicircular donor lenticule (hemi-nDSEK)—tamponading the ruptured Descemet while preserving the remaining healthy endothelium and avoiding the uninvolved visual axis. Within 1 week, best corrected visual acuity (BCVA) improved from counting fingers to 20/72 and pain resolved (Fig. 2, left). At 4 months, hydrops had fully resolved with minimal inferotemporal scarring and a clear central cornea, with BCVA of 20/32 (Fig. 2, right). At 1 year, the patient’s vision remained stable, and no further intervention was required. Traditional management of hydrops is primarily medical while awaiting spontaneous resolution, but interventional methods to expedite resolution including gas tamponade and pre-Descemet sutures are increasingly used.4–6 The efficacy of these methods is variable, and scarring resulting from hydrops may require penetrating keratoplasty (PK) to improve vision. The rationale for using EK is two-fold. First, resolution is expedited by mechanically sealing the tear in DM with healthy tissue, a longer-lasting, more robust option than intracameral gas. Second, the healthy donor endothelium actively pumps excess fluid from the host stroma. FIGURE 1. Above: Slit-lamp photograph at initial presentation, demonstrating inferotemporal corneal hydrops. Below: High-resolution anterior segment OCT (Spectralis, Heidelberg Engineering GmbH, Heidelberg, Germany) showing area of ruptured Descemet membrane and gross corneal thickening with bullae with the bandage contact lens in situ.

Research paper thumbnail of Femtolaser-assisted Keratoplasty: Surgical Outcomes and Benefits

Journal of EuCornea, 2020

Femtosecond laser technology has evolved as an alternative method to make surgical incisions in k... more Femtosecond laser technology has evolved as an alternative method to make surgical incisions in keratoplasty. The use of this approach has a number of purported advantages that may lead to superior clinical outcomes. However, there remains a low uptake of the femtolaser-assisted keratoplasty within public healthcare, and incongruity remains between perceived expert opinion on the presence and significance of superior clinical outcomes based on available data. This review is registered publicly on the Open Science Framework registry and aims to evaluate the evidence base on femtolaser-assisted keratoplasty and its comparison with manual trephination in intraoperative and postoperative outcomes. Over 2000 studies were screened and critically appraised in the field of keratoplasty, using multiple databases. 17 studies were included via predetermined criteria for full analysis. The studies covered interventional research into penetrating keratoplasty (PK), deep anterior lamellar keratoplasty (DALK), and posterior lamellar keratoplasty (PLK). The results of this review show that PK studies shared a trend of improved visual outcomes with the femtolaser, and evidence for earlier suture removal. Complication rates were similar. When used for DALK, studies showed some evidence of improved visual outcomes with the femtolaser, and evidence for earlier suture removal, reduced intraoperative complications and increased wound healing activity. The use in Descemet's membrane endothelial keratoplasty (DMEK) showed reduced graft detachment whereas in Descemet's stripping automated endothelial keratoplasty (DSAEK) the results were limited. Overall, this review shows a trend that the use of the femtolaser may improve clinical outcomes in PK, DALK and DMEK. However, it was also clear that in order to corroborate the superiority of femtolaser-assisted keratoplasty versus manual methods, further research is required.

Research paper thumbnail of REVIEW Clinical applications of corneal confocal microscopy

Abstract: Corneal confocal microscopy is a novel clinical technique for the study of corneal cell... more Abstract: Corneal confocal microscopy is a novel clinical technique for the study of corneal cellular structure. It provides images which are comparable to in-vitro histochemical techniques delineating corneal epithelium, Bowman’s layer, stroma, Descemet’s membrane and the corneal endothelium. Because, corneal confocal microscopy is a non invasive technique for in vivo imaging of the living cornea it has huge clinical potential to investigate numerous corneal diseases. Thus far it has been used in the detection and management of pathologic and infectious conditions, corneal dystrophies and ecstasies, monitoring contact lens induced corneal changes and for pre and post surgical evaluation (PRK, LASIK and LASEK, flap evaluations and Radial Keratotomy), and penetrating keratoplasty. Most recently it has been used as a surrogate for peripheral nerve damage in a variety of peripheral neuropathies and may have potential in acting as a surrogate marker for endothelial abnormalities.

Research paper thumbnail of Reducing the burden of ocular surface disease with serum eye drops

Research paper thumbnail of Phase 2 Randomized, Double-Masked, Vehicle-Controlled Trial of Recombinant Human Nerve Growth Factor for Neurotrophic Keratitis

Ophthalmology, Jan 10, 2018

To evaluate the safety and efficacy of topical recombinant human nerve growth factor (rhNGF) for ... more To evaluate the safety and efficacy of topical recombinant human nerve growth factor (rhNGF) for treating moderate-to-severe neurotrophic keratitis (NK), a rare degenerative corneal disease resulting from impaired corneal innervation. Phase 2 multicenter, randomized, double-masked, vehicle-controlled trial. Patients with stage 2 (moderate) or stage 3 (severe) NK in 1 eye. The REPARO phase 2 study assessed safety and efficacy in 156 patients randomized 1:1:1 to rhNGF 10 μg/ml, 20 μg/ml, or vehicle. Treatment was administered 6 drops per day for 8 weeks. Patients then entered a 48- or 56-week follow-up period. Safety was assessed in all patients who received study treatment, whereas efficacy was by intention to treat. Corneal healing (defined as <0.5-mm maximum diameter of fluorescein staining in the lesion area) was assessed by masked central readers at week 4 (primary efficacy end point) and week 8 (key secondary end point) of controlled treatment. Corneal healing was reassessed ...

Research paper thumbnail of Impact of graft thickness on visual acuity after Descemet's stripping endothelial keratoplasty

British Journal of Ophthalmology, 2012

Objective To evaluate the relationship, over time, between central graft thickness and visual acu... more Objective To evaluate the relationship, over time, between central graft thickness and visual acuity following Descemet&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s stripping endothelial keratoplasty (DSEK). Methods A retrospective analysis of 70 consecutive cases of DSEK. All donor lenticules were dissected manually. Serial postoperative measurements of central graft and total corneal thicknesses were made using anterior segment optical coherence tomography. Visual acuity, refraction and patient demographics were collected from case notes. The correlation between central graft thickness and visual acuity at serial time points was calculated. Results The median age at surgery was 75 years (lower quartile (LQ) 66, upper quartile (UQ) 83, range 36-90 years). Nineteen eyes were excluded from statistical analysis, leaving 51 eyes of 46 patients remaining. Last follow-up occurred a median of 12 months postoperatively (LQ 6, UQ 23, range 4-38 months). The median preoperative visual acuity was 0.71 logarithm of the minimum angle of resolution (logMAR), improving to 0.34 logMAR postoperatively (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001, n=43). Median graft thickness decreased from 209 μm at day 1 to 142 μm at last follow-up…

Research paper thumbnail of Shaikh Ali Hossain

BMJ, 2016

Shaikh Ali Hossain (“Ali”) worked as consultant psychiatrist at South Ockendon Psychiatric Hospit... more Shaikh Ali Hossain (“Ali”) worked as consultant psychiatrist at South Ockendon Psychiatric Hospital, Essex, from 1974 till 1994. He specialised in learning disabilities. He took over this post at a time when the hospital had faced a major inquiry, …

Research paper thumbnail of 20 Gy External Beam Radiotherapy Can Stablise Vision in Patients with Subfoveal Choroidal Neovascular Membranes in the First 12 Months

Investigative Ophthalmology & Visual Science, 2002

Research paper thumbnail of Temporal Release of Matrix Metalloproteinases in Human Microbial Keratitis

Investigative Ophthalmology & Visual Science, 2009

Research paper thumbnail of Microbial keratitis—the true costs of a silent pandemic?

Research paper thumbnail of The Potential of Limbal Neurosphere Cells to Differentiate into Retinal Cell Phenotypes

Research paper thumbnail of Early Use Of Infliximab Improves Outcomes In Patients With Rheumatoid Arthritis Associated Sight Threatening Ocular Surface Inflammation

Research paper thumbnail of The future of refractive surgery: presbyopia treatment, can we dispense with our glasses?

Refractive error remains the leading cause for visual impairment. With an aging world population,... more Refractive error remains the leading cause for visual impairment. With an aging world population, presbyopia is the leading refractive deficit. In many parts of the developed world, the average person can spend half of their lives in presbyopia [1]. With increasing digital demands, there is an increasing dependence on accommodation and presbyopic symptoms can appear as early as the 30s age group [2]. With refractive error affecting most of the world’s population at some point in their lives, it is not surprising that surgical approaches to correct refractive error have gained interest. Over the past 30 years, we saw an explosion in the variety of surgical approaches with their own relative nuances in technique, risks and benefits [2]. In this edition, Ang et al. [3], overview the advancements in refractive surgery over the past three decades and provide an insight, beyond 2020. The authors cover the rich variety of procedures, showing how surgery has evolved and how it can correct v...

Research paper thumbnail of Effect of Posterior Donor Lenticule Thickness on Optical Abberations and Visual outcome with time after Descemet Stripping Endothelial Keratoplasty (DSEK)

Investigative Ophthalmology & Visual Science, 2011

Research paper thumbnail of Seasonal Allergic Conjunctivitis Is Associated With Increased Conjunctival Epithelial Height & Upregulation of Both PAR 2 & HSP 70 Protein

Research paper thumbnail of L-selectin And Cd34 Are Expressed By Human Stromal Keratocytes

Research paper thumbnail of Diagnostic Technologies in Ophthalmology

Diagnostic Technologies in Ophthalmology, 2012

Research paper thumbnail of The role of type 4 pilus, flagella and type III secretion system in the interactions between Pseudomonas aeruginosa bacteria and corneal fibroblasts in human microbial keratitis

Investigative Ophthalmology & Visual Science, 2016

Microbial keratitis (MK) is a leading cause of blindness in the developing world. Pseudomonas aer... more Microbial keratitis (MK) is a leading cause of blindness in the developing world. Pseudomonas aeruginosa (PA) is the most common pathogen isolated from contact lens related MK, and is usually associated with significant visual complications. The intact corneal epithelium forms a strong barrier to bacterial penetration into deeper tissue, and only when bacteria reach the stroma, through a breach in the epithelium, does a typical ulcer develop, with stromal suppuration and necrosis. Since corneal fibroblasts are one of the most prominent cellular components in the stroma, they probably have an important role in the pathogenesis of corneal ulceration. The aim of this study was to establish an in vitro model of PA microbial keratitis in order to examine the microbiological, biochemical and ultrastructural changes associated with live infection of primary human corneal fibroblasts (hCF) with PA, and to assess the role of these cells in the initiation and progression of the pathogenesis of the disease. Human corneal fibroblast monolayers were infected with bacteria, and bacterial association was assessed at 3, 6 and 9h, bacterial invasion was assessed at 9h and cytokine profiles were assessed at 9 and 24 h post challenge. Host cell death was assessed at 9h using a lactate dehydrogenase assay (LDH). Gentamicin was added at 3h to eliminate all extra cellular bacteria and limit pathogen induced effects, and bacterial replication and survival and its effect on host cell viability were assessed. Induction of cytokine and matrix metalloproteinase (MMP) production by hCF in response to PA infection was assessed by a sandwich immunoassay and a gelatine zymography. To examine the interactions of PA with the cornea as an organ, donor corneal buttons remaining after DSEK were incubated in a medium inoculated with PA for 3-9h, then processed for scanning and transmission electron microscopy. Scanning and Transmission Electron Micrographs (SEM/TEM) ii of bacterial association and invasion of corneal cells were acquired and showed that bacteria associated to superficial epithelial cells but only invaded and colonized the stroma in the presence of a mechanical breach to the epithelial basement membrane. PAO1 bacteria caused monolayer disruption within 24h with all infective doses (10 1-10 8 CFU/mL). PAO1 associated to hCF in a dose-and time-dependant manner utilizing type IV pilus and flagella. Bacterial internalization was detected by the gentamicin assay, which also demonstrated the ability of PAO1 to survive and replicate within the fibroblasts, and was dependant on the SRC tyrosine kinase and the actin microfilament system, where internalisation was diminished when these systems were inhibited. Cytotoxicity was observed by 9h post challenge, and was reliant on bacterial type III secretion system and flagella, where mutant bacterial strains induced less cytotoxicity. The more virulent PA14 bacteria induced more cytotoxicity than PAO1. The presence of intracellular bacteria did not affect cell viability in the presence of gentamicin. In response to PAO1 infection, hCF produced the pro-inflammatory IL-1β and GM-CSF, although GM-CSF seems to be released later than IL-1β as shown by protecting the cells with gentamicin 3h post challenge. Infection with PA14 caused an earlier and more potent cytokine production than PAO1, reflecting the pattern of cytotoxicity. Bacterial components did not have a significant effect on cytokine production by corneal fibroblasts. Cytokine production was partly reliant on bacterial type III secretion system and flagella, and wild type PA14 strains induced an earlier and more potent IL-1β production by infected corneal fibroblasts. Gelatine zymography showed that hCF produce specific MMPs in response to live PA challenge for 24h, and these MMPs were not released in response to treatment with individual bacterial components and virulence factors. Bacteria alone produced alkaline protease, a bacterial MMP. Sandwich immunoassays showed that MMP-1, MMP-2, MMP-3 and MMP-9 were produced by infected fibroblasts to a level similar to uninfected cells. Gentamicin protected cells produced more MMPs than unprotected cells.

Research paper thumbnail of Personal hygiene risk factors for contact lens-related microbial keratitis

BMJ Open Ophthalmology

ObjectiveMicrobial keratitis is a sight-threatening complication of contact lens wear, which affe... more ObjectiveMicrobial keratitis is a sight-threatening complication of contact lens wear, which affects thousands of patients and causes a significant burden on healthcare services. This study aims to identify compliance with contact lens care recommendations and identify personal hygiene risk factors in patients who develop contact lens-related microbial keratitis.Methods and analysisA case–control study was conducted at the University Hospital Southampton Eye Casualty from October to December 2015. Two participant groups were recruited: cases were contact lens wearers presenting with microbial keratitis and controls were contact lens wearers without infection. Participants underwent face-to-face interviews to identify lens wear practices, including lens type, hours of wear, personal hygiene and sleeping and showering in lenses. Univariate and multivariate regression models were used to compare groups.Results37 cases and 41 controls were identified. Showering in contact lenses was ide...

Research paper thumbnail of Response to: 'Comment on: ‘Dupilumab-associated ocular surface disease: presentation, management and long-term sequelae’

Research paper thumbnail of Peripheral Corneal Hydrops Secondary to Pellucid Marginal Degeneration Managed With a Manually Dissected Semicircular Endothelial Keratoplasty Lenticule

Cornea, Jan 16, 2018

To the Editor: We read with interest Tu’s1 report of using endothelial keratoplasty (EK) in a cas... more To the Editor: We read with interest Tu’s1 report of using endothelial keratoplasty (EK) in a case of nonresolving acute corneal hydrops secondary to keratoconus. EK has previously been used to treat other similar causes of corneal edema due to tears in Descemet’s membrane (DM), such as corneal hydrops in keratoglobus2 and late corneal decompensation secondary to obstetric forceps trauma.3 We report the case of a 42-year-old woman with peripheral corneal hydrops secondary to pellucid marginal degeneration (Fig. 1), successfully managed with EK. She had previously had a similar episode in her fellow eye, complicated by corneal perforation. After 6 weeks of nonresolution despite standard conservative treatment and air tamponade, the patient continued to be in severe pain and the threat of impending perforation led us to perform non-Descemet stripping EK with a manually dissected semicircular donor lenticule (hemi-nDSEK)—tamponading the ruptured Descemet while preserving the remaining healthy endothelium and avoiding the uninvolved visual axis. Within 1 week, best corrected visual acuity (BCVA) improved from counting fingers to 20/72 and pain resolved (Fig. 2, left). At 4 months, hydrops had fully resolved with minimal inferotemporal scarring and a clear central cornea, with BCVA of 20/32 (Fig. 2, right). At 1 year, the patient’s vision remained stable, and no further intervention was required. Traditional management of hydrops is primarily medical while awaiting spontaneous resolution, but interventional methods to expedite resolution including gas tamponade and pre-Descemet sutures are increasingly used.4–6 The efficacy of these methods is variable, and scarring resulting from hydrops may require penetrating keratoplasty (PK) to improve vision. The rationale for using EK is two-fold. First, resolution is expedited by mechanically sealing the tear in DM with healthy tissue, a longer-lasting, more robust option than intracameral gas. Second, the healthy donor endothelium actively pumps excess fluid from the host stroma. FIGURE 1. Above: Slit-lamp photograph at initial presentation, demonstrating inferotemporal corneal hydrops. Below: High-resolution anterior segment OCT (Spectralis, Heidelberg Engineering GmbH, Heidelberg, Germany) showing area of ruptured Descemet membrane and gross corneal thickening with bullae with the bandage contact lens in situ.

Research paper thumbnail of Femtolaser-assisted Keratoplasty: Surgical Outcomes and Benefits

Journal of EuCornea, 2020

Femtosecond laser technology has evolved as an alternative method to make surgical incisions in k... more Femtosecond laser technology has evolved as an alternative method to make surgical incisions in keratoplasty. The use of this approach has a number of purported advantages that may lead to superior clinical outcomes. However, there remains a low uptake of the femtolaser-assisted keratoplasty within public healthcare, and incongruity remains between perceived expert opinion on the presence and significance of superior clinical outcomes based on available data. This review is registered publicly on the Open Science Framework registry and aims to evaluate the evidence base on femtolaser-assisted keratoplasty and its comparison with manual trephination in intraoperative and postoperative outcomes. Over 2000 studies were screened and critically appraised in the field of keratoplasty, using multiple databases. 17 studies were included via predetermined criteria for full analysis. The studies covered interventional research into penetrating keratoplasty (PK), deep anterior lamellar keratoplasty (DALK), and posterior lamellar keratoplasty (PLK). The results of this review show that PK studies shared a trend of improved visual outcomes with the femtolaser, and evidence for earlier suture removal. Complication rates were similar. When used for DALK, studies showed some evidence of improved visual outcomes with the femtolaser, and evidence for earlier suture removal, reduced intraoperative complications and increased wound healing activity. The use in Descemet's membrane endothelial keratoplasty (DMEK) showed reduced graft detachment whereas in Descemet's stripping automated endothelial keratoplasty (DSAEK) the results were limited. Overall, this review shows a trend that the use of the femtolaser may improve clinical outcomes in PK, DALK and DMEK. However, it was also clear that in order to corroborate the superiority of femtolaser-assisted keratoplasty versus manual methods, further research is required.

Research paper thumbnail of REVIEW Clinical applications of corneal confocal microscopy

Abstract: Corneal confocal microscopy is a novel clinical technique for the study of corneal cell... more Abstract: Corneal confocal microscopy is a novel clinical technique for the study of corneal cellular structure. It provides images which are comparable to in-vitro histochemical techniques delineating corneal epithelium, Bowman’s layer, stroma, Descemet’s membrane and the corneal endothelium. Because, corneal confocal microscopy is a non invasive technique for in vivo imaging of the living cornea it has huge clinical potential to investigate numerous corneal diseases. Thus far it has been used in the detection and management of pathologic and infectious conditions, corneal dystrophies and ecstasies, monitoring contact lens induced corneal changes and for pre and post surgical evaluation (PRK, LASIK and LASEK, flap evaluations and Radial Keratotomy), and penetrating keratoplasty. Most recently it has been used as a surrogate for peripheral nerve damage in a variety of peripheral neuropathies and may have potential in acting as a surrogate marker for endothelial abnormalities.

Research paper thumbnail of Reducing the burden of ocular surface disease with serum eye drops

Research paper thumbnail of Phase 2 Randomized, Double-Masked, Vehicle-Controlled Trial of Recombinant Human Nerve Growth Factor for Neurotrophic Keratitis

Ophthalmology, Jan 10, 2018

To evaluate the safety and efficacy of topical recombinant human nerve growth factor (rhNGF) for ... more To evaluate the safety and efficacy of topical recombinant human nerve growth factor (rhNGF) for treating moderate-to-severe neurotrophic keratitis (NK), a rare degenerative corneal disease resulting from impaired corneal innervation. Phase 2 multicenter, randomized, double-masked, vehicle-controlled trial. Patients with stage 2 (moderate) or stage 3 (severe) NK in 1 eye. The REPARO phase 2 study assessed safety and efficacy in 156 patients randomized 1:1:1 to rhNGF 10 μg/ml, 20 μg/ml, or vehicle. Treatment was administered 6 drops per day for 8 weeks. Patients then entered a 48- or 56-week follow-up period. Safety was assessed in all patients who received study treatment, whereas efficacy was by intention to treat. Corneal healing (defined as <0.5-mm maximum diameter of fluorescein staining in the lesion area) was assessed by masked central readers at week 4 (primary efficacy end point) and week 8 (key secondary end point) of controlled treatment. Corneal healing was reassessed ...

Research paper thumbnail of Impact of graft thickness on visual acuity after Descemet's stripping endothelial keratoplasty

British Journal of Ophthalmology, 2012

Objective To evaluate the relationship, over time, between central graft thickness and visual acu... more Objective To evaluate the relationship, over time, between central graft thickness and visual acuity following Descemet&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s stripping endothelial keratoplasty (DSEK). Methods A retrospective analysis of 70 consecutive cases of DSEK. All donor lenticules were dissected manually. Serial postoperative measurements of central graft and total corneal thicknesses were made using anterior segment optical coherence tomography. Visual acuity, refraction and patient demographics were collected from case notes. The correlation between central graft thickness and visual acuity at serial time points was calculated. Results The median age at surgery was 75 years (lower quartile (LQ) 66, upper quartile (UQ) 83, range 36-90 years). Nineteen eyes were excluded from statistical analysis, leaving 51 eyes of 46 patients remaining. Last follow-up occurred a median of 12 months postoperatively (LQ 6, UQ 23, range 4-38 months). The median preoperative visual acuity was 0.71 logarithm of the minimum angle of resolution (logMAR), improving to 0.34 logMAR postoperatively (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001, n=43). Median graft thickness decreased from 209 μm at day 1 to 142 μm at last follow-up…

Research paper thumbnail of Shaikh Ali Hossain

BMJ, 2016

Shaikh Ali Hossain (“Ali”) worked as consultant psychiatrist at South Ockendon Psychiatric Hospit... more Shaikh Ali Hossain (“Ali”) worked as consultant psychiatrist at South Ockendon Psychiatric Hospital, Essex, from 1974 till 1994. He specialised in learning disabilities. He took over this post at a time when the hospital had faced a major inquiry, …

Research paper thumbnail of 20 Gy External Beam Radiotherapy Can Stablise Vision in Patients with Subfoveal Choroidal Neovascular Membranes in the First 12 Months

Investigative Ophthalmology & Visual Science, 2002

Research paper thumbnail of Temporal Release of Matrix Metalloproteinases in Human Microbial Keratitis

Investigative Ophthalmology & Visual Science, 2009

Research paper thumbnail of Microbial keratitis—the true costs of a silent pandemic?

Research paper thumbnail of The Potential of Limbal Neurosphere Cells to Differentiate into Retinal Cell Phenotypes

Research paper thumbnail of Early Use Of Infliximab Improves Outcomes In Patients With Rheumatoid Arthritis Associated Sight Threatening Ocular Surface Inflammation

Research paper thumbnail of The future of refractive surgery: presbyopia treatment, can we dispense with our glasses?

Refractive error remains the leading cause for visual impairment. With an aging world population,... more Refractive error remains the leading cause for visual impairment. With an aging world population, presbyopia is the leading refractive deficit. In many parts of the developed world, the average person can spend half of their lives in presbyopia [1]. With increasing digital demands, there is an increasing dependence on accommodation and presbyopic symptoms can appear as early as the 30s age group [2]. With refractive error affecting most of the world’s population at some point in their lives, it is not surprising that surgical approaches to correct refractive error have gained interest. Over the past 30 years, we saw an explosion in the variety of surgical approaches with their own relative nuances in technique, risks and benefits [2]. In this edition, Ang et al. [3], overview the advancements in refractive surgery over the past three decades and provide an insight, beyond 2020. The authors cover the rich variety of procedures, showing how surgery has evolved and how it can correct v...

Research paper thumbnail of Effect of Posterior Donor Lenticule Thickness on Optical Abberations and Visual outcome with time after Descemet Stripping Endothelial Keratoplasty (DSEK)

Investigative Ophthalmology & Visual Science, 2011

Research paper thumbnail of Seasonal Allergic Conjunctivitis Is Associated With Increased Conjunctival Epithelial Height & Upregulation of Both PAR 2 & HSP 70 Protein

Research paper thumbnail of L-selectin And Cd34 Are Expressed By Human Stromal Keratocytes

Research paper thumbnail of Diagnostic Technologies in Ophthalmology

Diagnostic Technologies in Ophthalmology, 2012

Research paper thumbnail of The role of type 4 pilus, flagella and type III secretion system in the interactions between Pseudomonas aeruginosa bacteria and corneal fibroblasts in human microbial keratitis

Investigative Ophthalmology & Visual Science, 2016

Microbial keratitis (MK) is a leading cause of blindness in the developing world. Pseudomonas aer... more Microbial keratitis (MK) is a leading cause of blindness in the developing world. Pseudomonas aeruginosa (PA) is the most common pathogen isolated from contact lens related MK, and is usually associated with significant visual complications. The intact corneal epithelium forms a strong barrier to bacterial penetration into deeper tissue, and only when bacteria reach the stroma, through a breach in the epithelium, does a typical ulcer develop, with stromal suppuration and necrosis. Since corneal fibroblasts are one of the most prominent cellular components in the stroma, they probably have an important role in the pathogenesis of corneal ulceration. The aim of this study was to establish an in vitro model of PA microbial keratitis in order to examine the microbiological, biochemical and ultrastructural changes associated with live infection of primary human corneal fibroblasts (hCF) with PA, and to assess the role of these cells in the initiation and progression of the pathogenesis of the disease. Human corneal fibroblast monolayers were infected with bacteria, and bacterial association was assessed at 3, 6 and 9h, bacterial invasion was assessed at 9h and cytokine profiles were assessed at 9 and 24 h post challenge. Host cell death was assessed at 9h using a lactate dehydrogenase assay (LDH). Gentamicin was added at 3h to eliminate all extra cellular bacteria and limit pathogen induced effects, and bacterial replication and survival and its effect on host cell viability were assessed. Induction of cytokine and matrix metalloproteinase (MMP) production by hCF in response to PA infection was assessed by a sandwich immunoassay and a gelatine zymography. To examine the interactions of PA with the cornea as an organ, donor corneal buttons remaining after DSEK were incubated in a medium inoculated with PA for 3-9h, then processed for scanning and transmission electron microscopy. Scanning and Transmission Electron Micrographs (SEM/TEM) ii of bacterial association and invasion of corneal cells were acquired and showed that bacteria associated to superficial epithelial cells but only invaded and colonized the stroma in the presence of a mechanical breach to the epithelial basement membrane. PAO1 bacteria caused monolayer disruption within 24h with all infective doses (10 1-10 8 CFU/mL). PAO1 associated to hCF in a dose-and time-dependant manner utilizing type IV pilus and flagella. Bacterial internalization was detected by the gentamicin assay, which also demonstrated the ability of PAO1 to survive and replicate within the fibroblasts, and was dependant on the SRC tyrosine kinase and the actin microfilament system, where internalisation was diminished when these systems were inhibited. Cytotoxicity was observed by 9h post challenge, and was reliant on bacterial type III secretion system and flagella, where mutant bacterial strains induced less cytotoxicity. The more virulent PA14 bacteria induced more cytotoxicity than PAO1. The presence of intracellular bacteria did not affect cell viability in the presence of gentamicin. In response to PAO1 infection, hCF produced the pro-inflammatory IL-1β and GM-CSF, although GM-CSF seems to be released later than IL-1β as shown by protecting the cells with gentamicin 3h post challenge. Infection with PA14 caused an earlier and more potent cytokine production than PAO1, reflecting the pattern of cytotoxicity. Bacterial components did not have a significant effect on cytokine production by corneal fibroblasts. Cytokine production was partly reliant on bacterial type III secretion system and flagella, and wild type PA14 strains induced an earlier and more potent IL-1β production by infected corneal fibroblasts. Gelatine zymography showed that hCF produce specific MMPs in response to live PA challenge for 24h, and these MMPs were not released in response to treatment with individual bacterial components and virulence factors. Bacteria alone produced alkaline protease, a bacterial MMP. Sandwich immunoassays showed that MMP-1, MMP-2, MMP-3 and MMP-9 were produced by infected fibroblasts to a level similar to uninfected cells. Gentamicin protected cells produced more MMPs than unprotected cells.

Research paper thumbnail of Personal hygiene risk factors for contact lens-related microbial keratitis

BMJ Open Ophthalmology

ObjectiveMicrobial keratitis is a sight-threatening complication of contact lens wear, which affe... more ObjectiveMicrobial keratitis is a sight-threatening complication of contact lens wear, which affects thousands of patients and causes a significant burden on healthcare services. This study aims to identify compliance with contact lens care recommendations and identify personal hygiene risk factors in patients who develop contact lens-related microbial keratitis.Methods and analysisA case–control study was conducted at the University Hospital Southampton Eye Casualty from October to December 2015. Two participant groups were recruited: cases were contact lens wearers presenting with microbial keratitis and controls were contact lens wearers without infection. Participants underwent face-to-face interviews to identify lens wear practices, including lens type, hours of wear, personal hygiene and sleeping and showering in lenses. Univariate and multivariate regression models were used to compare groups.Results37 cases and 41 controls were identified. Showering in contact lenses was ide...

Research paper thumbnail of Response to: 'Comment on: ‘Dupilumab-associated ocular surface disease: presentation, management and long-term sequelae’