Search

Corneal transplantation surgery faces several fundamental problems, including graft failure, especially in complicated cases, and a marked shortage of human donor corneas. The purpose of this revie...

Summary: Background: We undertook a Grand Challenges in Global Eye Health prioritisation exercise to identify the key issues that must be addressed to improve eye health in the context of an ageing population, to eliminate persistent inequities in health-care access, and to mitigate widespread resource limitations. Methods: Drawing on methods used in previous Grand Challenges studies, we used a multi-step recruitment strategy to assemble a diverse panel of individuals from a range of disciplines relevant to global eye health from all regions globally to participate in a three-round, online, Delphi-like, prioritisation process to nominate and rank challenges in global eye health. Through this process, we developed both global and regional priority lists. Findings: Between Sept 1 and Dec 12, 2019, 470 individuals complete round 1 of the process, of whom 336 completed all three rounds (round 2 between Feb 26 and March 18, 2020, and round 3 between April 2 and April 25, 2020) 156 (46%) of 336 were women, 180 (54%) were men. The proportion of participants who worked in each region ranged from 104 (31%) in sub-Saharan Africa to 21 (6%) in central Europe, eastern Europe, and in central Asia. Of 85 unique challenges identified after round 1, 16 challenges were prioritised at the global level; six focused on detection and treatment of conditions (cataract, refractive error, glaucoma, diabetic retinopathy, services for children and screening for early detection), two focused on addressing shortages in human resource capacity, five on other health service and policy factors (including strengthening policies, integration, health information systems, and budget allocation), and three on improving access to care and promoting equity. Interpretation: This list of Grand Challenges serves as a starting point for immediate action by funders to guide investment in research and innovation in eye health. It challenges researchers, clinicians, and policy makers to build collaborations to address specific challenges. Funding: The Queen Elizabeth Diamond Jubilee Trust, Moorfields Eye Charity, National Institute for Health Research Moorfields Biomedical Research Centre, Wellcome Trust, Sightsavers, The Fred Hollows Foundation, The Seva Foundation, British Council for the Prevention of Blindness, and Christian Blind Mission. Translations: For the French, Spanish, Chinese, Portuguese, Arabic and Persian translations of the abstract see Supplementary Materials section.

Navid Hakim,1 Philippa Longmore,1 Victor H Hu1,2 1Eye Department, Mid Cheshire NHS Hospitals Foundation Trust, Crewe, UK; 2International Centre for Eye Health, London School of Hygiene and Tropical Medicine, London, UKCorrespondence: Navid HakimEye Department, Mid Cheshire NHS Hospitals Foundation Trust, Crewe, CW1 4QJ, UKTel +44 7540492816Email navid.hakim@nhs.netIntroduction: An ophthalmic remote consultation clinic was implemented due to the COVID-19 pandemic for stable patients under the corneal service in a district general hospital in Cheshire, UK. Patients were reviewed either by video or telephone consultation. The purpose of this survey was to assess patient satisfaction with this service.Methods: Consecutive patients who were seen by remote consultation between September 2020 and November 2020 were identified. Approval for the survey was gained from the hospital Patient Experience and Survey department. A telephone survey was conducted between 4 and 8 weeks after the initial patient appointment. Data were obtained for patient demographic information, appointment details and patient satisfaction with their appointment, including preference for subsequent appointments and open feedback.Results: Eighty-four remote consultations were identified and 51 (60.7%) patients completed the survey: 48 (94.1%) reported satisfaction with their remote consultation; 36 (70.5%) reported satisfaction for a subsequent remote consultation; and 33 (64.7%) patients reported they preferred being seen remotely rather than face-to-face. Qualitative data on patients’ thoughts about the service could be categorised into 4 themes: satisfaction with the interaction and service, conveniency, lack of clinical examination and satisfaction with the service given the current pandemic circumstances.Conclusion: This survey has shown that patients were satisfied with their remote consultation and the majority thought it was an acceptable method of consultation. This also allowed patients to continue being seen during a period of COVID-19 lockdown and reduce patient footfall through the hospital. Overall feedback indicated very high levels of patient satisfaction with this service.Keywords: COVID-19, ophthalmology, telemedicine, cornea

To investigate if topical chlorhexidine 0.2%, which is low cost and easy to formulate, is noninferior to topical natamycin 5% for the treatment of filamentous fungal keratitis.Randomized controlled, single-masked, noninferiority clinical trial.Adults attending a tertiary-level ophthalmic hospital in Nepal with filamentous fungal infection confirmed on smear or confocal microscopy.Participants were randomly allocated to receive topical chlorhexidine 0.2% or topical natamycin 5%. Primary analysis (intention-to-treat) was by linear regression, using baseline logarithm of the minimum angle of resolution (logMAR) best spectacle-corrected visual acuity (BSCVA) and treatment arm as prespecified covariates. Mixed fungal-bacterial infections were excluded from the primary analysis but included in secondary analyses and secondary safety-related outcomes. The noninferiority margin was 0.15 logMAR. This trial was registered with ISRCTN, number ISRCTN14332621.The primary outcome measure was BSCVA at 3 months. Secondary outcome measures included perforation or therapeutic penetrating keratoplasty by 90 days.Between June 3, 2019, and November 9, 2020, 354 eligible participants were enrolled and randomly assigned: 178 to chlorhexidine and 176 to natamycin. Primary outcome data were available for 153 and 151 of the chlorhexidine and natamycin groups, respectively. Of these, mixed bacterial-fungal infections were found in 20 cases (12/153 chlorhexidine, 8/151 natamycin) and excluded from the primary analysis. Therefore, 284 patients were assessed for the primary outcome (141 chlorhexidine, 143 natamycin). We did not find evidence to suggest chlorhexidine was noninferior to natamycin and in fact found strong evidence to suggest that natamycin-treated participants had significantly better 3-month BSCVA than chlorhexidine-treated participants, after adjusting for baseline BSCVA (regression coefficient, -0.30; 95% confidence interval [CI], -0.42 to -0.18; P0.001). There were more perforations and emergency corneal grafts in the chlorhexidine arm (24/175, 13.7%) than in the natamycin arm (10/173, 5.8%; P = 0.018, mixed infections included), whereas natamycin-treated cases were less likely to perforate or require an emergency corneal graft, after adjusting for baseline ulcer depth (odds ratio, 0.34; 95% CI, 0.15-0.79; P = 0.013).Treatment with natamycin is associated with significantly better visual acuity, with fewer adverse events, compared with treatment with chlorhexidine. Natamycin remains the preferred first-line monotherapy treatment for filamentous fungal keratitis.

ObjectiveFungal keratitis is a major ophthalmic public health problem, particularly in low-income and middle-income countries. The options for treating fungal keratitis are limited. Our study aimed to describe the outcomes of using chlorhexidine 0.2% eye-drops as additional treatment in the management of patients with recalcitrant fungal keratitis.MethodsThis study was nested within a large cohort study of people presenting with microbial keratitis in Uganda. We enrolled patients with recalcitrant fungal keratitis not improving with topical natamycin 5% and commenced chlorhexidine 0.2%. Follow-up was scheduled for 3 months and 1 year. The main outcome measures were healing, visual acuity and scar size at final follow-up.ResultsThirteen patients were followed in this substudy. The patients were aged 27–73 years (median 43 years). Filamentous fungi were identified by microscopy of corneal scrape samples in all cases. Isolated organisms included Aspergillus spp, Fusarium spp, Candida spp, Bipolaris spp and Acremoninum spp. At the final follow-up, nine patients (75%) had healed; three had vision of better than 6/18. Three patients lost their eyes due to infection. In the remaining nine cases, corneal scarring was variable ranging from 4.6 to 9.4 mm (median 6.6 mm, IQR 5.9–8.0 mm); of these five had dense scars, three had moderate scars and one had a mild scar. None of the patients demonstrated signs of chlorhexidine toxicity during the follow-up.ConclusionChlorhexidine 0.2% was found to be a useful sequential adjunctive topical antifungal in cases of fungal keratitis not responding to natamycin 5%, which warrants further evaluation.

IntroductionFungal infections of the cornea, fungal keratitis (FK), are challenging to treat. Current topical antifungals are not always effective and are often unavailable, particularly in low-income and middle-income countries where most cases occur. Topical natamycin 5% is usually first-line treatment, however, even when treated intensively, infections may progress to perforation of the eye in around a quarter of cases. Alternative antifungal medications are needed to treat this blinding disease.Chlorhexidine is an antiseptic agent with antibacterial and antifungal properties. Previous pilot studies suggest that topical chlorhexidine 0.2% compares favourably with topical natamycin. Full-scale randomised controlled trials (RCTs) of topical chlorhexidine 0.2% are warranted to answer this question definitively.Methods and analysisWe will test the hypothesis that topical chlorhexidine 0.2% is non-inferior to topical natamycin 5% in a two-arm, single-masked RCT. Participants are adults with FK presenting to a tertiary ophthalmic hospital in Nepal. Baseline assessment includes history, examination, photography, in vivo confocal microscopy and cornea scrapes for microbiology. Participants will be randomised to alternative topical antifungal treatments (topical chlorhexidine 0.2% and topical natamycin 5%; 1:1 ratio, 2–6 random block size). Patients are reviewed at day 2, day 7 (with reculture), day 14, day 21, month 2 and month 3. The primary outcome is the best spectacle corrected visual acuity (BSCVA) at 3 months. Primary analysis (intention to treat) will be by linear regression, with treatment arm and baseline BSCVA prespecified covariates. Secondary outcomes include epithelial healing time, scar/infiltrate size, ulcer depth, hypopyon size, perforation and/or therapeutic penetrating keratoplasty (corneal transplant), positive reculture rate (day 7) and quality of life (EuroQol-5 dimensions, WHO/PBD-VF20, WHOQOL-BREF).Ethics and disseminationThe Nepal Health Research Council, the Nepal Department of Drug Administration and the London School of Hygiene and Tropical Medicine ethics committee have approved the trial. The results will be presented at local and international meetings and submitted to peer-reviewed journals for publication.Trial registration numberISRCTN14332621; pre-results.

Importance In vivo confocal microscopy (IVCM) provides high-resolution images of the ocular surface and has been validated in trachomatous conjunctival scarring. Background This study used IVCM to identify parameters associated with clinical scarring progression. Design Prospective cohort study. Participants A total of 800 participants in Northern Tanzania with trachomatous scarring. Methods Participants underwent clinical examination, photography and IVCM at baseline and 24-months. Clinical progression of scarring was defined by comparing baseline and 24-month photographs. Masked grading of IVCM images was used to identify scarring at both time points. Multivariable logistic regression was used to assess factors associated with clinical progression. Main outcome measures Risk factors associated with clinical scarring progression. Results Clinical and IVCM assessment of 800 participants were performed at baseline, with 617 (77.1%) seen at 24-months. Of these, 438 of 617 (71.0%) had gradable IVCM images at both time points and 342 of 438 (78.1%) of these could be graded as showing definite clinical progression or no progression on image comparison. Clinical progression was found to occur in 79 of 342 (23.1%). After adjusting for age and sex, clinical scarring progression was strongly associated with a high IVCM connective tissue organization score at both baseline (odds ratio [OR] = 1.84 for each increase in scarring category; P = .002) and 24-months (OR = 1.60; P = .02). Dendritiform cells present at 24-months were strongly associated with clinical scarring progression after adjustment (OR = 2.62; P = .03). Conclusions and relevance Quantitative IVCM parameters, including connective tissue organization score and the presence of dendritiform cells, are associated with disease progression and may be useful markers in trachoma and other conjunctival fibrotic diseases.

Background In the Solomon Islands and Vanuatu, the sign trachomatous inflammation—follicular (TF) is common, but ocular infection with Chlamydia trachomatis is not. It is therefore debatable whether azithromycin mass drug administration (MDA), the recommended antibiotic treatment strategy for trachoma’s elimination as a public health problem, is necessary in this setting. We set out to estimate what proportion of adolescents were at risk of progression of trachomatous scarring. Methods A cross-sectional survey was undertaken of all children aged 10–14 years resident in communities identified as high-TF clusters during previous population-based mapping. Graders examined children for clinical evidence of trachomatous scarring, pannus, and Herbert’s pits (HPs) or limbal follicles in both eyes. A dried blood spot was collected from each child and tested for antibodies to C. trachomatis. Results A total of 492 children in 24 villages of the Solomon Islands and Vanuatu were examined. In total, 35/492 (7%) of children had limbal signs (pannus and/or HPs) plus any conjunctival scarring. And 9/492 (2%) had limbal signs and moderate or severe conjunctival scarring; 22% of children were anti-Pgp3 seropositive. Conclusions Few adolescents here are at risk of future complications from trachoma, supporting the conclusion that further antibiotic MDA is not currently required for trachoma elimination purposes in these settings., In Solomon Islands and Vanuatu communities in which active trachoma prevalence in children was previously high, prevalence of Herbert’s pits or pannus plus conjunctival scarring in 10–14-year-olds is low, suggesting risk of future trachomatous blindness here is also low.

Purpose: To describe the epidemiology of Microbial Keratitis (MK) in Uganda. Methods: We prospectively recruited patients presenting with MK at two main eye units in Southern Uganda between December 2016 and March 2018. We collected information on clinical history and presentation, microbiology and 3-month outcomes. Poor vision was defined as vision < 6/60). Results: 313 individuals were enrolled. Median age was 47 years (range 18–96) and 174 (56%) were male. Median presentation time was 17 days from onset (IQR 8–32). Trauma was reported by 29% and use of Traditional Eye Medicine by 60%. Majority presented with severe infections (median infiltrate size 5.2 mm); 47% were blind in the affected eye (vision < 3/60). Microbiology was available from 270 cases: 62% were fungal, 7% mixed (bacterial and fungal), 7% bacterial and 24% no organism detected. At 3 months, 30% of the participants were blind in the affected eye, while 9% had lost their eye from the infection. Delayed presentation (overall p = .007) and prior use of Traditional Eye Medicine (aOR 1.58 [95% CI 1.04–2.42], p = .033) were responsible for poor presentation. Predictors of poor vision at 3 months were: baseline vision (aOR 2.98 [95%CI 2.12–4.19], p < .0001), infiltrate size (aOR 1.19 [95%CI 1.03–1.36], p < .020) and perforation at presentation (aOR 9.93 [95% CI 3.70–26.6], p < .0001). Conclusion: The most important outcome predictor was the state of the eye at presentation, facilitated by prior use of Traditional Eye Medicine and delayed presentation. In order to improve outcomes, we need effective early interventions.

Background: Microbial keratitis (MK) frequently leads to sight-loss, especially when the infection is severe and/or appropriate treatment is delayed. The primary health system as an entry point plays a central role in facilitating and directing patient access to appropriate care. The purpose of this study was to describe the capacity of primary health centres in Uganda in managing MK. Methods: We carried out a rigorous assessment of primary health centres and mid-cadre training schools in South Western Uganda. Through interviews, checklists and a picture quiz, we assessed capacity and knowledge of MK management. In addition, we interviewed the heads of all the mid-cadre training schools to determine the level of eye health training provided in their curricula. Results: In total, 163 health facilities and 16 training schools were enrolled. Of the health facilities, only 6% had an Ophthalmic Clinical Officer. Only 12% of the health workers could make a diagnosis of MK based on the clinical signs in the picture quiz. Although 35% of the facilities had a microscope, none reported doing corneal scraping. None of the facilities had a stock of the recommended first line treatment options for MK (ciprofloxacin and natamycin eye drops). Among the training schools, 15/16 had an eye health component in the curriculum. However, the majority (56%) of tutors had no formal expertise in eye health. In 14/16 schools, students spent an average of two weeks in an eye unit. Conclusions: Knowledge among health workers and capacity of health facilities in diagnosis and management of MK was low. Training for eye health within mid-cadre training schools was inadequate. More is needed to close these gaps in training and capacity.

BackgroundMicrobial keratitis (MK) is a frequent cause of sight loss in sub-Saharan Africa. However, no studies have formally measured its impact on quality of life (QoL) in this context.MethodsAs part of a nested case–control design for risk factors of MK, we recruited patients presenting with MK at two eye units in Southern Uganda between December 2016 and March 2018 and unaffected individuals, individually matched for sex, age and location. QoL was measured using WHO Health-Related and Vision-Related QoL tools (at presentation and 3 months after start of treatment in cases). Mean QoL scores for both groups were compared. Factors associated with QoL among the cases were analysed in a linear regression model.Results215 case-controls pairs were enrolled. The presentation QoL scores for the cases ranged from 20 to 65 points. The lowest QoL was visual symptom domain; mean 20.7 (95% CI 18.8 to 22.7) and the highest was psychosocial domain; mean 65.6 (95% CI 62.5 to 68.8). At 3 months, QoL scores for the patients ranged from 80 to 90 points while scores for the controls ranged from 90 to 100. The mean QoL scores of the cases were lower than controls across all domains. Determinants of QoL among the cases at 3 months included visual acuity at 3 months and history of eye loss.ConclusionMK severely reduces QoL in the acute phase. With treatment and healing, QoL subsequently improves. Despite this improvement, QoL of someone affected by MK (even with normal vision) remains lower than unaffected controls.

Purpose The purpose of this study was to assess whether non-chlamydial bacterial infection is associated with progression of trachomatous scarring in adults. Methods This was a cohort study involving 800 participants in northern Tanzania who underwent clinical examination, photography, and conjunctival swab collection for microbiology over a 24-month period. Samples for microbiology were inoculated onto blood and chocolate agar, and Chlamydia trachomatis was detected by PCR. Progression was determined by comparison of baseline to 24-month photographs. Results C. trachomatis was detected in only four participants at baseline. At 24 months, 617 participants (77.1%) were followed up. Of those seen at 24 months, 452 could be reliably assessed. Definite scarring progression (progressors) was seen in 345 (55.9%); there was no progression (nonprogressors) in 107 (17.3%). Using combined baseline and 12-month microbiology results, progressors had significantly higher levels of commensal and pathogenic bacterial organisms detected compared with nonprogressors. After adjusting for age, baseline scarring, and ethnicity, there was weak evidence (P = 0.07) that the bacteria category was associated with scarring progression (commensal organisms only: odds ratio [OR] = 1.61; 95% confidence interval [CI]: 0.90 to 2.89; pathogenic organisms either with or without commensal: OR = 2.39; 95% CI: 1.10 to 5.16). Conclusion The findings were consistent with the possibility that trachomatous scarring in adults is associated with the presence of non-chlamydial bacterial organisms, particularly pathogenic organisms. C. trachomatis was detected very infrequently and may not be an important factor in the pathogenesis of scarring progression in adults. This has implications for trachoma control programs, which largely concentrate on reducing C. trachomatis levels and transmission.

Background: Traditional eye medicine (TEM) is frequently used to treat microbial keratitis (MK) in many parts of Africa. Few reports have suggested that this is associated with a worse outcome. We undertook this large prospective study to determine how TEM use impacts presentation and outcome of MK and to explore reasons why people use TEM for treatment in Uganda. Methods: In a mixed method prospective cohort study, we enrolled patients presenting with MK at the two main eye units in Southern Uganda between December 2016 and March 2018 and collected information on history, TEM use, microbiology and 3-month outcomes. We conducted qualitative interviews with patients, carers traditional healers on reasons why people use TEM. Outcome measures included presenting vision and at 3-months, comparing TEM Users versus Non-Users. A thematic coding framework was deployed to explore reasons for use of TEM. Results: Out of 313 participants enrolled, 188 reported TEM use. TEM Users had a delayed presentation; median presenting time 18 days versus 14 days, p= 0.005; had larger ulcers 5.6 mm versus 4.3 mm p=0.0005; a worse presenting visual acuity median logarithm of the minimum angle of resolution (Log MAR) 1.5 versus 0.6, p=0.005; and, a worse visual acuity at 3 months median Log MAR 0.6 versus 0.2, p=0.010. In a multivariable logistic regression model, distance from the eye hospital and delayed presentation were associated with TEM use. Reasons for TEM use included lack of confidence in conventional medicine, health system breakdown, poverty, fear of the eye hospital, cultural belief in TEM, influence from traditional healers, personal circumstances and ignorance. Conclusion: TEM users had poorer clinical presentation and outcomes. Capacity building of the primary health centres to improve access to eye care and community behavioural change initiatives against TEM use should be encouraged.

ObjectivePrediction errors are increased among patients presenting for cataract surgery post laser vision correction (LVC) as biometric relationships are altered. We investigated the prediction errors of five formulae among these patients.Methods and analysisThe intended refractive error was calculated as a sphero-cylinder and as a spherical equivalent for analysis. For determining the difference between the intended and postoperative refractive error, data were transformed into components of Long's formalism, before changing into sphero-cylinder notation. These differences in refractive errors were compared between the five formulae and to that of a control group using a Kruskal-Wallis test. An F-test was used to compare the variances of the difference distributions.Results22 eyes post LVC and 19 control eyes were included for analysis. Comparing both groups, there were significant differences in the postoperative refractive error (p=0.038). The differences between the intended and postoperative refractive error were greater in post LVC eyes than control eyes (p=0.012), irrespective of the calculation method for the intended refractive error (pConclusionBiometry calculations were less precise for patients who had LVC than patients without LVC. No particular biometry formula appears to be superior among patients post LVC.

AIM: To compare in vivo confocal microscopy (IVCM) with the histopathological examination of tissue and cellular changes in normal and diseased conjunctiva. METHODS: Participants underwent clinical examination and IVCM of the tarsal conjunctiva. A biopsy of the upper tarsal conjunctiva was collected and stained with tinctorial stains and by immunohistochemical staining for CD45 and CD83. Connective tissue scarring, inflammatory cell density and the presence of dendritiform cells were quantitatively assessed in a masked manner by both IVCM and histological assessments for comparative analysis. RESULTS: Thirty-four participants with severe trachomatous conjunctival scarring and 33 participants with healthy conjunctiva were recruited. The IVCM connective tissue scarring score was strongly associated with the histological grading of scarring (p

Introduction The phenotype and function of immune cells infiltrating the conjunctiva in scarring trachoma have yet to be fully characterized. We assessed tissue morphology and immunophenotype of cellular infiltrates found in trachomatous scarring compared to control participants. Methodology Clinical assessments and conjunctival biopsy samples were obtained from 34 individuals with trachomatous scarring undergoing trichiasis surgery and 33 control subjects undergoing cataract or retinal detachment surgery. Biopsy samples were fixed in buffered formalin and embedded in paraffin wax. Hematoxylin and eosin (H&E) staining was performed for assessment of the inflammatory cell infiltrate. Immunohistochemical staining of single markers on individual sections was performed to identify cells expressing CD3 (T-cells), CD4 (helper T-cells), CD8 (suppressor/cytotoxic T-cells and Natural Killer, NK, cells), NCR1 (NK cells), CD20 (B-cells), CD45 (nucleated hematopoietic cells), CD56 (NK and T-cells), CD68 (macrophages/monocytes) and CD83 (mature dendritic cells). The degree of scarring was assessed histologically using cross-polarized light to visualize collagen fibres. Principle Findings Scarring, regardless of clinical inflammation, was associated with increased inflammatory cell infiltrates on H&E and CD45 staining. Scarring was also associated with increased CD8+ and CD56+ cells, but not CD3+ cells, suggestive of a NK cell infiltrate. This was supported by the presence of NCR1+ cells. There was some increase in CD20+ cells, but no evidence for increased CD4+, CD68+ or CD83+ cells. Numerous CD45 negative cells were also seen in the population of infiltrating inflammatory cells in scarred conjunctiva. Disorganization of the normal collagen architecture was strongly associated with clinical scarring. Conclusions/Significance These data point to the infiltration of immune cells with a phenotype suggestive of NK cells in conjunctival trachomatous scarring. A large proportion of CD45 negative inflammatory cells were also present. Future work should seek to understand the stimuli leading to the recruitment of these cells and their role in progressive scarring., Author Summary Trachoma is initiated by repeated infection of the conjunctiva throughout childhood by the bacterium Chlamydia trachomatis (Ct). Conjunctival inflammation and scarring progress throughout the lives of many adults even in the absence of Ct infection, causing the eyelashes to turn inwards (trichiasis) and damage the cornea, resulting in severe pain and eventually leading to blindness. The factors sustaining the inflammation that drives scarring are not understood and there is no treatment to halt scarring progression. We sought to define the phenotypes of immune cells infiltrating the conjunctiva during trichiasis. Eyelid tissue from 34 individuals with trichiasis and 33 control individuals was stained with dyes or specific antibodies to distinguish immune cell subsets. Increased inflammatory cells were detected in individuals with trichiasis even when clinical signs of inflammation were not apparent. Staining of immune cell types pointed to an increased infiltration of natural killer cells in tissue from individuals with trichiasis. These cells may cause tissue damage through cytokine secretion and cell lysis. Surprisingly, a large number of infiltrating immune cells lacked the classical immune cell marker CD45. The phenotype and function of these CD45 negative cells and their role in scarring trachoma warrants further study.

Purpose To determine the accuracy of orthoptist referrals from a preschool-based vision screening program for children 3-4 years of age and to report the outcomes of referred children. Methods This was a retrospective review of records of participants in the preschool vision screening program in the Walsall, United Kingdom, area for the 2006-2007 school year. Screening examinations were performed by orthoptists and included assessment of visual acuity, ocular alignment, ocular motility, and stereoacuity. Results For the 2006-2007 school year, 2,830 of 3,623 children (78%) were screened, Of these, 413 were referred to the Hospital Eye Service. Comparison of the screening results and the Hospital Eye Service examination revealed that recorded visual acuities were similar in 81% of subjects and ocular alignment in 94%. Visual acuity was 6/9 or better at the hospital examination in 87% of referred children, with 46% requiring spectacle use only; 17% of referrals were diagnosed with amblyopia. Conclusions Although the Walsall vision screening program diverged from UK national guidelines by testing at an earlier age, there was no evidence that earlier screening led to a large number of incorrect referrals, and early screening may allow for better outcomes. Sensitivity of screening was not tested, and orthoptist screening in the United Kingdom is likely to be more accurate in this age group than nonspecialist or lay screening that is performed in many other areas.

Trachoma is the most common infectious cause of blindness and a major public health problem in many developing countries. It is caused by recurrent ocular infection with Chlamydia trachomatis in childhood, with conjunctival scarring seen later in life. The pathogenesis of trachomatous scarring, however, is poorly understood, and this study was carried out to investigate the immunofibrogenic correlates of trachomatous conjunctival scarring. A case-control study of 363 cases with conjunctival scarring and 363 control participants was conducted. Investigations included in vivo confocal microscopy (IVCM) assessment, quantitative real-time PCR gene expression, C. trachomatis detection, and nonchlamydial bacterial culture. Trachomatous scarring was found to be strongly associated with a proinflammatory, innate immune response with increased expression of psoriasin, interleukin-1β, tumor necrosis factor alpha, defensin-β4A, chemokine ligand 5, and serum amyloid A1. There was also differential expression of various modifiers of the extracellular matrix, including metalloproteinases 7, 9, 10, and 12, tissue inhibitor of matrix metalloproteinase 1, and secreted protein acidic cystein-rich-like 1. The expression of many of these genes was also significantly associated with the presence of nonchlamydial bacterial infection. These infections had a marked effect on conjunctival immune processes, including an increased inflammatory infiltrate and edema seen with IVCM. This study supports the possibility that the immunofibrogenic response in scarring trachoma is partly stimulated by nonchlamydial bacterial infection, which is characterized by the expression of innate factors.

The immunological basis of scarring trachoma is not well understood. It is unclear whether it is driven primarily through cell-mediated adaptive or epithelial-cell-derived innate responses. The purpose of this study was to investigate the expression of the inflammatory and fibrogenic mediators which may be involved. We conducted a cross-sectional survey of children living in an untreated trachoma-endemic community in Tanzania. The children were examined for signs of trachoma, and swabs were collected for bacteriological culture and RNA and DNA isolation. Chlamydia trachomatis was detected by the Amplicor PCR test. The expression of the following genes was measured by quantitative reverse transcription-PCR (RT-PCR): S100A7 , IL1B , IL17A , IL23A , CXCL5 , CCL18 , TLR2 , NLRP3 , KLRD1 , CTGF , and MMP9 . Four hundred seventy children under the age of 10 years were included. Follicular trachoma (TF) was detected in 65 children (14%), C. trachomatis was detected in 25 (5%), and bacterial pathogens were cultured in 161 (34%). TF was associated with significantly increased expression of S100A7 , IL17A , CCL18 , CXCL5 , and CTGF. Expression was increased further in the presence of papillary inflammation. Nonchlamydial bacterial infection was associated with increased expression of IL17A , CXCL5 , CCL18 , and KLRD1 . IL17A expression was associated with increased expression of S100A7 , CXCL5 , CCL18 , KLRD1 , and CTGF. These data are consistent with a role for IL-17A in orchestrating the proinflammatory response in trachoma. Its activity may be promoted either as part of the cell-mediated response or through innate pathways. It may drive a range of proinflammatory factors leading to excessive tissue damage and repair involving fibrosis.

Objective To characterize the tissue and cellular changes found in trachomatous scarring (TS) and inflammation using in vivo confocal microscopy (IVCM). Design Two complimentary case-control studies. Participants The first study included 363 cases with TS (without trichiasis), of whom 328 had IVCM assessment, and 363 control subjects, of whom 319 had IVCM assessment. The second study included 34 cases with trachomatous trichiasis (TT), of whom 28 had IVCM assessment, and 33 control subjects, of whom 26 had IVCM assessment. Methods All participants were examined with ×2.5 loupes. The IVCM examination of the upper tarsal conjunctiva was carried out with a Heidelberg Retina Tomograph 3 with the Rostock Cornea Module (Heidelberg Engineering GmbH, Dossenheim, Germany). Main Outcome Measures The IVCM images were graded in a masked manner using a previously published grading system evaluating the inflammatory infiltrate density; the presence or absence of dendritiform cells (DCs), tissue edema, and papillae; and the level of subepithelial connective tissue organization. Results Subjects with clinical scarring had a characteristic appearance on IVCM of well-defined bands and sheets of scar tissue visible. Similar changes were also seen in some clinically normal subjects consistent with subclinical scarring. Scarred subjects had more DCs and an elevated inflammatory infiltrate, even after adjusting for other factors, including the level of clinical inflammation. Cellular activity was usually seen only in or just below the epithelium, rarely being seen deeper than 30 μm from the surface. The presence of tissue edema was strongly associated with the level of clinical inflammation. Conclusions In vivo confocal microscopy can be quantitatively used to study inflammatory and scarring changes in the conjunctiva. Dendritic cells seem to be closely associated with the scarring process in trachoma and are likely to be an important target in antifibrotic therapies or the development of a chlamydial vaccine. The increased number of inflammatory cells seen in scarred subjects is consistent with the immunopathologic nature of the disease. The localization of cellular activity close to the conjunctival surface supports the view that the epithelium plays a central role in the pathogenesis of trachoma. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Trachoma is the commonest infectious cause of blindness. Recurrent episodes of infection with serovars A-C of Chlamydia trachomatis cause conjunctival inflammation in children who go on to develop scarring and blindness as adults. It was estimated that in 2002 at least 1.3 million people were blind from trachoma, and currently 40 million people are thought to have active disease and 8.2 million to have trichiasis. The disease is largely found in poor, rural communities in developing countries, particularly in sub-Saharan Africa. The WHO promotes trachoma control through a multifaceted approach involving surgery, mass antibiotic distribution, encouraging facial cleanliness and environmental improvements. This has been associated with significant reductions in the prevalence of active disease over the past 20 years, but there remain a large number of people with trichiasis who are at risk of blindness.

PURPOSE: To compare corneal endothelial cell loss after cataract surgery by phacoemulsification and by Aqualase. METHODS: This was a prospective, randomized study of 75 eyes of 75 patients undergoing cataract surgery. Patients were randomly assigned to receive either phacoemulsification or Aqualase for cataract removal. Specular microscopy was used to calculate endothelial cell counts preoperatively and 3 weeks and 6 months afterwards. Best-corrected visual acuity was also measured. The t-test was used to detect statistical significance. RESULTS: The mean endothelial cell loss was 8.1% in the phacoemulsification group and 6.8% in the Aqualase group. There was no statistically significant difference in the amount of endothelial cell loss or in visual outcome between the 2 groups. The number of Aqualase pulses tended to increase with nuclear density while the phacoemulsification time showed little variation with nuclear subtype. CONCLUSION: Endothelial cell loss after cataract surgery is similar whether phacoemulsification or Aqualase is used. Aqualase can be considered to be as safe as phacoemulsification with regard to corneal trauma and is a useful alternative especially for soft cataracts.

Necrotising fasciitis is a potentially devastating soft tissue infection with a significant fatality rate. Streptococcus is commonly associated, although the cause may be polymicrobial. Early recognition is essential and aggressive surgical intervention may be required to prevent the rapid spread of infection along fascial planes. We report an unusual case of necrotising fasciitis of the eyelids with spontaneous limitation of the area of necrosis.

Background Trachoma is the most common infectious cause of blindness worldwide. In-vivo confocal microscopy (IVCM) provides high-resolution images of the ocular surface. We have previously reported a grading system for the quantitative assessment of these images in scarring trachoma. We found that the presence of trachomatous scarring was strongly associated with the presence of dendritiform cells (DFCs). The present study assessed whether there is an association between DFCs and clinical progression in scarring. Methods Participants with trachomatous scarring in northern Tanzania were examined at baseline and 24 months (clinical assessment, photography, and IVCM of the upper tarsal conjunctiva). IVCM images were graded according to a validated grading system. Two independent observers identified scarring progression by comparing photographs taken at baseline and 24 months. Findings 800 participants were assessed clinically at baseline and 617 of them were re-examined at 24 months. There were 465 individuals who had photographs that could be confidently graded as having either progression or scarring, or not having progression. Progression was found to occur in 113 (24%) of the 465 individuals. IVCM images were obtained in 344 of these participants at baseline and 24 months, and 29 (8·4%) had DFCs present at baseline. The presence of DFCs at baseline was significantly associated with scarring progression (p=0·01), including adjustment for age and sex (p=0·03). Interpretation The presence of DFCs on IVCM images is associated with progressive trachomatous conjunctival scarring. DFCs are thought to represent dendritic cells, which have a central role in mediating the immune response and potentially in the pathogenesis of trachomatous scarring. The nature of these cells warrants further investigation, potentially as a novel antifibrotic therapeutic target. Funding Wellcome Trust senior research fellowship (to MB). National Institute for Health and Research academic clinical fellowship (to JH).

Objective To examine the reliability of clinical examination and in vivo confocal microscopy (IVCM) in distinguishing ocular surface squamous neoplasia (OSSN) from benign conjunctival lesions. Design Case-control study. Participants Sixty individuals with conjunctival lesions (OSSN and benign) and 60 age-matched controls with normal conjunctiva presenting to Kilimanjaro Christian Medical Centre, Moshi, Tanzania. Methods Participants were examined and photographed, and IVCM was performed. Patients with conjunctival lesions were offered excisional biopsy with histopathology and a human immunodeficiency virus (HIV) test. The IVCM images were read masked to the clinical appearance and pathology results. Images were graded for several specific features and given an overall categorization (normal, benign, or malignant). A group of 8 ophthalmologists were shown photographs of conjunctival lesions and asked to independently classify as OSSN or benign. Main Outcome Measures Comparison of the histopathology diagnosis with the clinical and IVCM diagnosis. Results Fifty-two cases underwent excisional biopsy with histopathology; 34 were on the OSSN spectrum, 17 were benign, and 1 was lymphoma. The cases and controls had comparable demographic profiles. Human immunodeficiency syndrome infection was more common in OSSN compared with benign cases (58.8% vs. 5.6%; odds ratio, 24.3, 95% confidence interval [CI], 2.8–204; P = 0.003). Clinically, OSSN lesions more frequently exhibited feeder vessels and tended to have more leukoplakia and a gelatinous appearance. Overall, the ophthalmologists showed moderate agreement with the histology result (average kappa = 0.51; 95% CI, 0.36–0.64). The masked grading of IVCM images reliably distinguished normal conjunctiva. However, IVCM was unable to reliably distinguish between benign lesions and OSSN because of an overlap in their appearance (kappa = 0.44; 95% CI, 0.32–0.57). No single feature was significantly more frequent in OSSN compared with benign lesions. The sensitivity and specificity of IVCM for distinguishing OSSN from benign conjunctival lesions were 38.5% and 66.7%, respectively. Conclusions In East Africa, conjunctival pathology is relatively common and can present significant diagnostic challenges for the clinician. In this study, neither clinical examination nor IVCM was found to reliably distinguish OSSN from benign conjunctival pathology because of an overlap in the features of these groups. Therefore, IVCM cannot currently replace histopathology, and management decisions should continue to rely on careful clinical assessment supported by histopathology as indicated.

Trachoma, caused by Chlamydia trachomatis (Ct), is the leading infectious blinding disease worldwide. Chronic conjunctival inflammation develops in childhood and leads to eyelid scarring and blindness in adulthood. The immune response to Ct provides only partial protection against re-infection, which can be frequent. Moreover, the immune response is central to the development of scarring pathology, leading to loss of vision. Here we review the current literature on both protective and pathological immune responses in trachoma. The resolution of Ct infection in animal models is IFNγ-dependent, involving Th1 cells, but whether this is the case in human ocular infection still needs to be confirmed. An increasing number of studies indicate that innate immune responses arising from the epithelium and other innate immune cells, along with changes in matrix metalloproteinase activity, are important in the development of tissue damage and scarring. Current trachoma control measures, which are centred on repeated mass antibiotic treatment of populations, are logistically challenging and have the potential to drive antimicrobial resistance. A trachoma vaccine would offer significant advantages. However, limited understanding of the mechanisms of both protective immunity and immunopathology to Ct remain barriers to vaccine development.

PURPOSE: To assess whether non-chlamydial bacterial infection is associated with trachomatous scarring in adults. METHODS: This was a case-control study of 360 cases with trachomatous scarring but without trichiasis, and 360 controls without scarring. All participants underwent clinical examination, and a swab was taken from the inferior conjunctival fornix. Samples were inoculated onto blood and chocolate agar later that day. RESULTS: Bacterial isolates were identified in 54.0% of cases compared with 34.6% of controls (P < 0.001). A multivariate logistic regression model adjusted for age and lack of education showed that scarring was associated with the presence of commensal organisms (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.01-2.09) and was strongly associated with the presence of pathogenic organisms (OR, 4.08; 95% CI, 1.59-10.45). There was an increasing prevalence of all bacterial isolates with increasing severity of scarring (P(trend) < 0.001). CONCLUSIONS: Trachomatous scarring is strongly associated with non-chlamydial bacterial infection compared with controls. The role of such infection with regard to scarring progression should be investigated and may have important implications for trachoma control strategies and prevention of blindness.

Endogenous endophthalmitis is a potentially blinding condition that occurs after the spread of organisms to the eye from a focus of infection elsewhere in the body. The holmium laser has gained increasing acceptance as being safe and effective for endoscopic lithotripsy. We report what we believe to be the first time endogenous endophthalmitis has been described as occurring after holmium laser lithotripsy, although it has been reported after extracorporeal shock wave lithotripsy. This 55-year-old woman developed infections in both eyes 2 to 3 weeks after the lithotripsy, with a good response to appropriate antibiotic treatment.

To assess the feasibility of determining intraocular lens (IOL) power by measurement of the central optic thickness using clinically available Scheimpflug imaging (Pentacam, Oculus).King's College Hospital Ophthalmology Department, London, United Kingdom.Sixty-seven eyes were assessed 1 month after uneventful phacoemulsification with in-the-bag implantation of AcrySof MA60AC IOLs (Alcon). The correlation between IOL thickness measurement and IOL power was calculated. Repeatability of central optic thickness measurement was determined from 10 successive scans of 4 patients.Within-subject standard deviation increased with the subject mean. The coefficient of variability was 1.4%. Measured lens thickness was highly correlated with lens power (R(2) = 0.94, P.001). Over the measured range, 95% confidence intervals varied between +/-0.83 diopters (D) and +/-0.92 D.Central IOL thickness measurements with the Pentacam Scheimpflug camera were highly repeatable and closely correlated with the known IOL power. The IOL power, calculated from a regression equation, is likely to be less than +/-1.00 D away from the actual power. Approximate in vivo IOL power determination is feasible with clinically available Scheimpflug imaging. This could be applied clinically in cases of unexplained postoperative refractive error.

Sclerochoroidal calcification is an uncommon condition. Metabolic evaluation and clinical examination are important to exclude associated systemic conditions such as the Bartter and Gitelman syndromes. It has been suggested that the lesions seen in sclerochoroidal calcification are calcium pyrophosphate dihydrate crystals. This report describes the first documented case in the UK of sclerochoroidal calcification associated with Gitelman syndrome and calcium pyrophosphate dihydrate deposition.

Visual loss associated with neuroretinitis (optic disc swelling with a macular star) should prompt questions about contact with cats.

Patients with disease of the visual pathway use all manner of ways to describe the sensory aberrations they are experiencing. An important part of an ophthalmologist's work is to try to gain a clear impression …

Highlights • Chlamydia trachomatis is the leading infectious cause of blindness. • Vaccine trials against ocular C. trachomatis infection were conducted in the 1960s. • Whole organism vaccines induced short-lived, strain-specific protective immunity. • Many correlates of protective immunity and pathology have been defined. • Important lessons have been learned to inform the development of a chlamydial vaccine., As well as being the most common bacterial sexually transmitted infection, Chlamydia trachomatis (Ct) is the leading infectious cause of blindness. The pathogenesis of ocular chlamydial infection (trachoma) is similar to that of genital infection. In the 1960s the efficacy of Ct vaccines against ocular infection was evaluated in major field trials in Saudi Arabia, Taiwan, The Gambia, India and Ethiopia. These trials showed that it was possible to induce short term immunity to ocular infection, and to reduce the incidence of inflammatory trachoma, by parenteral immunisation with killed or live whole organism vaccines. In one study, it was also shown that the incidence of scarring sequelae was reduced in vaccinated children. Detailed studies in non-human primates conducted at this time suggested that vaccination could lead to more severe inflammatory disease on subsequent challenge. Since that time there have been many studies on the immunological correlates of protective immunity and immunopathology in ocular Ct infection in humans and non-human primates, and on host genetic polymorphisms associated with protection from adverse sequelae. These have provided important information to guide the development and evaluation of a human Ct vaccine.