Type 1 and type 2 diabetes predisposed to higher Nd:YAG capsulotomy rates following cataract surgery: analysis of 53,471 consecutive cases.

OBJECTIVE: To assess the effect of diabetes type on Nd:YAG capsulotomy rates following cataract surgery. DESIGN: A retrospective cohort study. METHODS: All patients who underwent cataract extraction at the Department of Ophthalmology, Bristol Eye Hospital, Bristol, UK, between 2003 and 2017 were included. The Nd:YAG capsulotomy rate following cataract surgery was assessed and compared between nondiabetic, type 1 diabetes (T1D), and type 2 diabetes (T2D) patients. Multivariate Cox regression analysis controlling for age and sex was used to estimate hazard ratios for Nd:YAG laser capsulotomies. RESULTS: Included were 53,471 consecutive cataract surgeries. Overall, 42,651 eyes (79.8%) were in nondiabetic patients, 823 eyes (1.5%) were in T1D patients, and 9,997 eyes (18.7%) were in T2D patients. The mean follow-up time was 6.8 ± 4.2 years. In univariate analysis, the eyes of T1D patients (p < 0.001) and T2D patients (p = 0.003) had significantly higher Nd:YAG laser capsulotomy rates than the eyes of nondiabetic patients. In Cox regression analysis adjusted for the patient's age and sex, DM1 (HR 1.692, 95%CI 1.390-2.059, P<0.001) and DM2 (HR 1.157, 95%CI 1.075-1.244, P<0.001) remained significantly predictive for higher Nd:YAG laser capsulotomy rates. CONCLUSION: In our large cohort study, patients with T1D and T2D were predisposed to high risk for Nd:YAG capsulotomy following cataract surgery. This study may be beneficial and raise awareness regarding the assessment of posterior capsular opacification development in pseudophakic diabetic patients, particularly those with T1D. The significance of ophthalmology screening for diabetes individuals is further supported by this issue.

Incidence of Acanthamoeba Keratitis in the United Kingdom in 2015: A Prospective National Survey.

PURPOSE: The aims of this study were to quantify the incidence of Acanthamoeba keratitis (AK) in the United Kingdom and investigate risk factors and management parameters. METHODS: This was a prospective population-based study from January to December 2015 through the British Ophthalmic Surveillance Unit. Data were collected on demographics, clinical features, and management. Incidence rates were calculated from estimates of population and contact lens (CL) user numbers. Statistical analysis compared annualized incidences per million and altered risk ratios for AK with the England and Wales 24 months 1997/1998 to 1998/1999 study. RESULTS: The study identified 124 AK cases, an overall incidence of 2.35 per million. CL wearers accounted for 108 of 124 cases (87%), in whom the AK incidence was 26.94 per million. Herpes keratitis was initially misdiagnosed in 25 of 124 cases (20.2%). The highest incidence of AK was among planned replacement soft CL (PRSCL) wearers (50.65 per million), 7-fold greater than for daily disposable CL (DDSCL) users (7.24 per million). There was a significant increase in AK incidence ( P < 0.001) compared with both 1997/1998 [risk ratio 1.92, 95% confidence interval (CI) 1.38-2.66] and 1998/1999 (risk ratio 2.13, 95% CI 1.52-2.98) together with a higher incidence per million CL users of 26.94 versus 21.14 (1997/1998) and 17.53 (1998/1999). CONCLUSIONS: This study provides the first published data on the nationwide incidence of AK in the United Kingdom. The findings confirm an increasing incidence of AK, particularly among contact lens wearers since 1997/1998 to 1998/1999. PRSCLs were identified as a significant risk factor compared with DDSCLs. Misdiagnosis and treatment delays remain an ongoing problem for patients with AK.

Acanthamoeba keratitis: Molecular typing of Acanthamoeba species directly from ocular tissue.

This report explores the molecular profiling of Acanthamoeba spp. from individuals in the UK suffering from a debilitating, sight-threatening disease of the cornea known as Acanthamoeba keratitis (AK). Seventy ocular samples from individuals undergoing investigations for AK were sent to the Scottish Microbiology Reference Laboratories (SMiRL), Glasgow during 2017-2019, and subjected to DNA extraction followed by in-depth molecular typing using a nested PCR/bi-directional sequencing approach. Of the 70 samples tested, 40 were PCR-positive. Of these, 32 were successfully sequenced and assigned to two of 23 existing genotypes termed T1 to T23. Molecular profiling of the 32 samples highlighted two genotypes, namely T3 (n = 3) and T4 (n = 29). For those 29 samples identified as the T4 genotype, a sub-genotype (T4A-T4H) was recorded: T4A (n = 18); T4B (n = 5); T4C (n = 1); T4E (n = 4); and T4F (n = 1). This study highlights that the T4 genotype and T4A subtype are the predominant molecular variants to cause ocular disease in the UK. Gaining in-depth information on the molecular profiling of Acanthamoeba spp. is essential to increase our understanding of the source(s) of infection, transmission pathways, and potential associations with clinical outcomes for this rare, yet potentially debilitating ocular disease.

Use of corneal cross-linking beyond keratoconus: a systemic literature review.

PURPOSE: The success of corneal collagen cross-linking in altering keratoconus' clinical course has driven a search for further uses of this procedure. This literature review aims to analyze the scientific evidence available for the benefit of cross-linking in the management of ophthalmic diseases other than progressive keratoconus or ectasia induced by corneal refractive procedures. METHODS: A systemic literature review. RESULTS: We reviewed 97 studies. We found that collagen cross-linking can limit the progression of several other corneal ectasias, thus reducing and limiting the need for keratoplasty. Collagen cross-linking also can reduce the refractive power of the cornea and can be considered for a moderate degree of bacterial keratitis or when the organism is unidentified, which is refractive to antibiotics alone. However, the comparative rarity of these procedures has limited the extent of evidence. In fungal, Acanthamoeba, and herpes virus keratitis, the evidence is inconclusive of the safety and efficacy of cross-linking. CONCLUSION: Current clinical data is limited, and laboratory data has not fully correlated with published clinical data.

Modified "Top-up sandwich" technique for the management of corneal perforations: A case report and a literature review.

Purpose: We describe a modified technique for managing a peripheral, non-infected, corneal perforation using a "Sandwich" technique that combines posterior lamellar keratoplasty, an amniotic membrane patch and a Gundersen conjunctival flap. Observations: A 75-year-old female patient presented with Sjogren's syndrome-related corneal perforation. A mini-Descemet stripping automated endothelial keratoplasty (DSAEK) graft (5 mm) was introduced into the anterior chamber and was mobilized to plug the perforation. Then, two amniotic membrane patches were stacked over the perforation and glued. Finally, the whole area was covered with a Gundersen conjunctival flap, mobilized from the inferior conjunctiva and secured in place using interrupted 10-0 nylon sutures. A step-by-step guide is also described. At three months, the final visual acuity was 6/9. A literature review revealed ten cases in which a posterior lamellar graft was effectively employed to treat corneal perforations. Conclusions and Importance: We described a modified approach for treating peripheral corneal perforation surgically. This "sandwich" approach is simple to replicate and can give quick healing with few visual repercussions. Our detailed guide may be utilized to obtain similar results and may be added to the array of treatment options for peripheral corneal perforation.

Intraocular lens power calculation in patients with irregular astigmatism.

PURPOSE: Accurate intraocular lens (IOL) calculation in subjects with irregular astigmatism is challenging. This study evaluated the accuracy of using Scheimpflug-derived central 2-mm equivalent keratometry reading (EKR) values for IOL calculation in irregular astigmatism. METHODS: This retrospective study included subjects (31 eyes of 30 patients) who underwent cataract surgery and IOL calculation using the 2-mm central EKR methods. We compared prediction error (PE) and absolute PE (APE) outcomes using SRK/T and Barrett Universal II formulas for keratometry data obtained from the IOLMaster 500 and Pentacam (anterior corneal sim k) devices. RESULTS: Cataract surgery and IOL calculation using the 2-mm central EKR methods resulted in improved visual acuity (uncorrected: from 1.13 ± 0.38 to 0.65 ± 0.46 logMar, p < 0.01; best-corrected: from 0.45 ± 0.24 to 0.26 ± 0.20 logMar, p < 0.01) after surgery. The percentage of subjects with best-corrected visual acuity of 6/6 was 22%, < 6/9 was 58%, and < 6/12 was 71%. For both the SRK/T and the Barrett formulas, the PE was similar to those obtained by IOLMaster (> 0.14) but lower than those obtained by the anterior corneal sim k (p < 0.02). IOLMaster provided keratometry reading in only 23/31 (74.1%) of cases. CONCLUSIONS: The use of Scheimpflug central 2-mm EKR for IOL calculation in irregular astigmatism was beneficial in terms of visual acuity improvement. It had comparable refractive prediction performance to the IOLMaster 500 and better than the anterior corneal sim K. The 2-mm EKR method can be used when IOLMaster cannot provide a reliable reading in abnormal corneas.

Peripheral blood immune cell profiling of acute corneal transplant rejection.

Acute rejection (AR) of corneal transplants (CT) has a profound effect on subsequent graft survival but detailed immunological studies in human CT recipients are lacking. In this multi-site, cross-sectional study, clinical details and blood samples were collected from adults with clinically diagnosed AR of full-thickness (FT)-CT (n = 35) and posterior lamellar (PL)-CT (n = 21) along with Stable CT recipients (n = 177) and adults with non-transplanted corneal disease (n = 40). For those with AR, additional samples were collected 3 months later. Immune cell analysis was performed by whole-genome microarrays (whole blood) and high-dimensional multi-color flow cytometry (peripheral blood mononuclear cells). For both, no activation signature was identified within the B cell and T cell repertoire at the time of AR diagnosis. Nonetheless, in FT- but not PL-CT recipients, AR was associated with differences in B cell maturity and regulatory CD4+ T cell frequency compared to stable allografts. These data suggest that circulating B cell and T cell subpopulations may provide insights into the regulation of anti-donor immune response in human CT recipients with differing AR risk. Our results suggest that, in contrast to solid organ transplants, genetic or cellular assays of peripheral blood are unlikely to be clinically exploitable for prediction or diagnosis of AR.

Progression of Pediatric Keratoconus After Corneal Cross-Linking: A Systematic Review and Pooled Analysis.

PURPOSE: Corneal collagen cross-linking (CXL) is an effective treatment to slow down keratoconus (KC) progression in adults. Several studies have also shown efficacious outcomes in pediatric populations, yet no systematic analysis has been performed and no accepted definition for progression is available in children after CXL. This study aimed to establish the most commonly used criteria for progression and to conduct a systematic review of the literature with pooled analysis to assess children's keratoconus progression after CXL. METHODS: A systemic literature review combined with pooled analysis was performed on full-length studies of KC after CXL treatment in a pediatric population and the methods used to report progression were analyzed. RESULTS: Thirty-seven studies (2078 eyes) were identified on the rates of KC progression after CXL. The most common method to report progression was increased Kmax, Kmean, or Ksteep by ≥1.0 diopter (78.3% of studies). Using these criteria, the mean pooled progression rate after epithelium-off CXL was 9.9% (95% confidence interval: 6.1% -14.6%, total pooled sample size: 1508 eyes) with high heterogeneity between studies [I 2 = 86.48% (95% confidence interval: 80.98 - 90.39), P < 0.0001]. CONCLUSIONS: When considering KC progression after CXL in children, with an increase in Kmax, Kmean, or Ksteep ≥ 1.0 diopter, the progression risk was roughly 10%. We encourage clear quantitative reporting of KC progression in future studies evaluating CXL efficacy in pediatric populations.

Corneal Transplant Follow-up Study II: a randomised trial to determine whether HLA class II matching reduces the risk of allograft rejection in penetrating keratoplasty.

PURPOSE: A randomised trial to test the hypothesis that human leucocyte antigen (HLA) class II matching reduces the risk of allograft rejection in high-risk penetrating keratoplasty (PK). METHODS: All transplants were matched for HLA class I antigens (≤2 mismatches at the A and B loci) and corneas were allocated to patients by cohort minimisation to achieve 0, 1 or 2 HLA class II antigen mismatches. The corneal transplants (n=1133) were followed for 5 years. The primary outcome measure was time to first rejection episode. RESULTS: Cox regression analysis found no influence of HLA class II mismatching on risk of immunological rejection (HR 1.13; 95% CI 0.79 to 1.63; p=0.51). The risk of rejection in recipients older than 60 years was halved compared with recipients ≤40 years (HR 0.51; 95% CI 0.36 to 0.73; p=0.0003). Rejection was also more likely where cataract surgery had been performed after PK (HR 3.68; 95% CI 1.95 to 6.93; p<0.0001). In univariate analyses, preoperative factors including chronic glaucoma (p=0.02), vascularisation (p=0.01), inflammation (p=0.03), ocular surface disease (p=0.0007) and regrafts (p<0.001) all increased the risk of rejection. In the Cox model, however, none of these factors was individually significant but rejection was more likely where≥2 preoperative risk factors were present (HR 2.11; 95% CI 1.26 to 3.47; p<0.003). CONCLUSIONS: HLA class II matching, against a background of HLA class I matching, did not reduce the risk of allograft rejection. Younger recipient age, the presence of ≥2 preoperative risk factors and cataract surgery after PK all markedly increased the risk of allograft rejection. TRIAL REGISTRATION NUMBER: ISRCTN25094892.

Reducing visible aerosol generation during phacoemulsification in the era of Covid-19.

OBJECTIVE: To assess potential methods of reducing visible aerosol generation during clear corneal phacoemulsification surgery in the era of Covid-19. METHODS: Aerosol generation during phacoemulsification was assessed using a model comprising a human cadaveric corneoscleral rim mounted on an artificial anterior chamber. Typical phacoemulsification settings were used and visible aerosol production was recorded using high-speed 4K camera. Aerosolisation was evaluated under various experimental settings: Two different phacoemulsification tip sizes (2.2, 2.75 mm), varying levels of corneal moisture, the use of suction and blowing air in the surgical field, the use of hydroxypropyl methylcellulose (HPMC) coating of the cornea with a static and moving tip. RESULTS: This model demonstrates visible aerosol generation during phacoemulsification with a 2.75-mm phacoemulsification tip. No visible aerosol was noted with a 2.2-mm tip. The presence of visible aerosol was unrelated to corneal wetting. Suction in close proximity to the aerosol plume did not impact on its dispersion. Blowing air redirected the aerosol plume toward the ocular surface. Visible aerosol production was abolished when HPMC was used to coat the cornea. This effect lasted for an average of 67 ± 8 s in the static model. Visible aerosol generation was discerned during movement of the 2.2-mm tip toward the corneal wound. CONCLUSIONS: We demonstrate visible aerosol production in the setting of a model of clear corneal phacoemulsification. Visible aerosol can be reduced using a 2.2-mm phacoemulsification tip and reapplying HPMC every minute during phacoemulsification.

High-risk Corneal Transplantation: Recent Developments and Future Possibilities.

Human corneal transplantation (keratoplasty) is typically considered to have superior short- and long-term outcomes and lower requirement for immunosuppression compared to solid organ transplants because of the inherent immune privilege and tolerogenic mechanisms associated with the anterior segment of the eye. However, in a substantial proportion of corneal transplants, the rates of acute rejection and/or graft failure are comparable to or greater than those of the commonly transplanted solid organs. Critically, while registry data and observational studies have helped to identify factors that are associated with increased risk of corneal transplant failure, the extent to which these risk factors operate through enhancing immune-mediated rejection is less clear. In this overview, we summarize a range of important recent clinical and basic insights related to high-risk corneal transplantation, the factors associated with graft failure, and the immunological basis of corneal allograft rejection. We highlight critical research areas from which continued progress is likely to drive improvements in the long-term survival of high-risk corneal transplants. These include further development and clinical testing of predictive risk scores and assays; greater use of multicenter clinical trials to optimize immunosuppressive therapy in high-risk recipients and robust clinical translation of novel, mechanistically-targeted immunomodulatory and regenerative therapies that are emerging from basic science laboratories. We also emphasize the relative lack of knowledge regarding transplant outcomes for infection-related corneal diseases that are common in the developing world and the potential for greater cross-pollination and synergy between corneal and solid organ transplant research communities.

An 11-year analysis of microbial keratitis in the South West of England using brain-heart infusion broth.

BACKGROUND: The aims of this study were to identify the organisms responsible for microbial keratitis, as identified by corneal scrape using brain-heart infusion broth, trends over time and antimicrobial sensitivities, over an 11-year period at two eye units in the South West of England; Bristol Eye Hospital and Royal United Hospital, Bath. METHODS: All corneal scrapes performed and sent for microbiological analysis between 4th April 2006 and 31st October 2017 at the two eye units were retrospectively reviewed. First-line treatment was monotherapy with levofloxacin 0.5% and second-line treatment was a combination of cefuroxime 5% and gentamicin 1.5%. Both direct and enrichment cultures were used. RESULTS: In total, 2614 corneal scrapes from 2116 patients (1082 female, mean age 47.7 ± 21.2 years) were identified. 38.1% (n = 996) were culture positive and 1195 organisms were cultured. In all, 91.6% were bacteria (69.4% were gram-positive, 30.6% gram-negative). Coagulase-negative Staphylococci (CoNS) were the most commonly cultured organism (n = 430). Pseudomonas aeruginosa was the most commonly identified gram-negative organism (n = 189). In total, 6.9% (n = 83) of organisms cultured were fungi. In all, 1.4% (n = 17) were acanthamoeba. There was no statistically significant trend in the organisms observed over the study period. Sensitivity testing confirmed reasonable sensitivity to the empiric antibiotics used in clinical practice. CONCLUSIONS: This is the first report on microbial keratitis trends in the South West of England. Virulent organisms were likely to be detected on direct culture, whereas low virulent organisms such as CoNS were more likely to be detected on enrichment alone. Antibiotic sensitivity testing confirmed fluoroquinolone monotherapy as appropriate first-line treatment.

Peripheral ulcerative keratitis with corneal melt as the primary presentation in a case of human immunodeficiency virus.

Peripheral ulcerative keratitis (PUK) is an aggressive, potentially sight-threatening cause for peripheral corneal thinning. It is thought to be the result of immune complex deposition at the limbus, resulting in corneal inflammation and stromal melt. We present a case of a 43-year-old female patient of African origin, presenting with PUK and associated corneal perforation as the primary presentation of HIV infection. An urgent tectonic deep anterior lamellar keratoplasty was performed under general anaesthesia with excellent outcome. The patient was referred to the sexual health clinic and anti-retroviral treatment was initiated. This case is to the best of our knowledge the first report from the UK of PUK with corneal perforation as the primary presentation of HIV infection. As highlighted in this report, infection with HIV may initially be silent; therefore, it is vital to consider HIV infection when dealing with PUK of unknown aetiology.

Corneal transplant follow-up study II (CTFS II): a prospective clinical trial to determine the influence of HLA class II matching on corneal transplant rejection: baseline donor and recipient characteristics.

PURPOSE: To describe a study to determine the influence of HLA class II matching on allograft rejection of high-risk, full-thickness corneal transplants. METHODS: A prospective, longitudinal, clinical trial (ISRCTN25094892) with a primary outcome measure of time to first clinically determined rejection episode. Tissue typing used DNA-based techniques. Corneas were allocated to patients with ≤2 human leucocyte antigen (HLA) class I antigen mismatches by cohort minimisation to achieve 0, 1 or 2 HLA class II (HLA-DR) antigen mismatches. Transplants were to be followed up at 6 months and then annually on the anniversary of surgery for 5 years. Power calculations estimated a sample size of 856 transplants to detect a 0.1 difference in probability of rejection at 1 year between HLA class II matched and mismatched transplants at the 5% level of significance with 80% power. RESULTS: To allow for loss to follow-up, 1133 transplants in 980 patients were accrued to the study between 3 September 1998 and 2 June 2011. 17% of transplants had 0 HLA-DR mismatches. The most frequent indication was bullous keratopathy, accounting for 27% of transplants and 54% of the transplants were regrafts. Median waiting time for a matched graft was 3 months. Donor and recipient characteristics were distributed evenly across the study groups. CONCLUSION: Recruitment to the CFS II has closed with 1077/1133 transplants meeting all the study criteria. Follow-up has been completed and final analysis of the data has started. TRIAL REGISTRATION NUMBER: ISRCTN25094892 andUKCRNID9871, Pre-results.

Outcomes of sphincterotomy for small pupil phacoemulsification.

PURPOSE: Sphincterotomy, an alternative to iris hooks or pupil stretching, is a technique that can aid in small pupil phacoemulsification. The incidence of post-operative complications of this procedure, however, has not been studied. Our study evaluates the post-operative outcomes of phacoemulsification surgery with adjunctive pupillary sphincterotomy. METHODS: We conducted a retrospective review of case notes and Medisoft ® electronic record of patients that had undergone simultaneous sphincterotomy, phacoemulsification and intraocular lens (IOL) implantation by a single surgeon between March 2012 and February 2017. Our main outcome measures were post-operative ocular hypertension (IOP > 21 mmHg), uveitis and cystoid macular oedema (CMO). RESULTS: A total of 114 eyes of 114 patients were included in this study. The mean age was 81.2 years (range: 26-100). All patients had uncomplicated surgery. Transient (<1 month) ocular hypertension developed in five (4%) eyes. Sustained ocular hypertension (>1 month) occurred in one (1%) eye, which had pre-existing glaucoma. All four (4%) eyes that developed a persistent uveitis (>1 month) resolved with topical therapy except for one eye with a history of uveitis. The 6 (5%) eyes that developed CMO had a history significant for uveitis (n = 4), diabetic macular oedema (n = 1) and epiretinal membrane (n = 1). All CMO maculae resolved to their baseline. CONCLUSION: The incidence of post-operative complications following uncomplicated phacoemulsification and IOL implantation with pupillary sphincterotomy is low. The most important predisposing factors for development of a complication are ocular co-morbidities such as glaucoma, uveitis and the presence of a macular pathology.

The use of miltefosine in the management of refractory Acanthamoeba keratitis.

Acanthamoeba keratitis (AK) is a sight threatening infection most commonly affecting contact lens wearers. The authors report a case of intractable A.polyphaga and A.castellanii, with extensive intraocular spread, managed using oral miltefosine. A 59-year old male contact lens wearer was referred to the tertiary corneal service at Bristol Eye Hospital. Vision was hand movements on the left and 6/6 on the right. Clinical examination was consistent with left AK (confirmed by corneal scrape). Management included biguanide (polyhexamethylene biguanide (PHMB) 0.02%, later 0.06%) and diamidine (hexamidine 0.1%). Further treatment included imidazole (guttae voriconazole, oral posaconazole) and fortified biguanide (chlorhexidine 0.2%). Therapeutic PKP was performed. Microscopy revealed Acanthamoeba throughout host stroma. Corneal scrape and anterior chamber tap revealed persistent infection with Acanthamoeba. Intracameral voriconazole was administered twice. Clinically there was scleritis, with concerns regarding posterior segment involvement. There was a severe necrotic keratitis with almost complete corneal melt, requiring enucleation. Oral miltefosine was commenced to reduce the risk of transmission of Acanthamoeba beyond ocular structures at the time of the enucleation. Histopathological analysis detected A.polyphaga and A.castellanii in vitreous but not retina, choroid or optic nerve suggesting that infection had not progressed posteriorly through the ocular structures and the central nervous system was not involved. The use of miltefosine as a component of combination anti-parasitic therapy is associated with long-term survival in cases of Acanthamoeba infection of the central nervous system. This case reports its first systemic use in the United Kingdom in a case of severe intractable AK with intraocular spread.

Stability of visual outcome between 2 and 5 years following corneal transplantation in the UK.

BACKGROUND AND AIMS: Many studies of corneal transplantation focus on graft failure or rejection as endpoints, or report visual outcomes at one postoperative time point. We aimed to study the stability of visual outcomes between 2 and 5 years following corneal transplantation. METHODS: All patients with keratoconus (868) or Fuchs endothelial dystrophy (FED) (569) receiving their first corneal transplant for visual purposes in the UK between January 2003 and December 2009 were included. The probability of visual improvement or deterioration (gain or loss of ≥2 Snellen lines, respectively) between 2 and 5 years after keratoplasty was modelled by multivariable logistic regression. RESULTS: The majority of keratoconus patients with a penetrating keratoplasty (PK) or deep anterior lamellar keratoplasty maintained their visual acuity (651/868; 75%) while 15% (133/868) improved and 10% (84/868) deteriorated. Similarly, most patients with FED who received a PK maintained their vision (395/569; 70%) while 18% (105/569) improved and 12% (68/569) deteriorated.

Comparison of In Vivo Confocal Microscopy, PCR and Culture of Corneal Scrapes in the Diagnosis of Acanthamoeba Keratitis.

PURPOSE: Acanthamoeba keratitis (AK) is an uncommon but serious corneal infection, in which delayed diagnosis carries a poor prognosis. Conventional culture requires a long incubation period and has low sensitivity. Polymerase chain reaction (PCR) and in vivo confocal microscopy (IVCM) are available alternative diagnostic modalities that have increasing clinical utility. This study compares confocal microscopy, PCR, and corneal scrape culture in the early diagnosis of AK. METHODS: We reviewed the case notes of patients with a differential diagnosis of AK between June 2016 and February 2017 at the Bristol Eye Hospital, United Kingdom. Clinical features at presentation, and results of IVCM, PCR, and corneal scrape cultures were analyzed. RESULTS: A total of 25 case records were reviewed. AK was diagnosed in 14 patients (15 eyes). Based on the definition of "definite AK," the diagnostic sensitivities of IVCM, PCR, and corneal scrape cultures were 100% [95% confidence interval (CI), 63.1%-100%], 71.4% (95% CI, 41.9%-91.6%) and 33.3% (95% CI, 9.9%-65.1%), respectively. The 3 methods showed a specificity of 100% and a positive predictive value of 100%. Using a reference standard of only positive corneal cultures, IVCM, and PCR had a sensitivity of 100% (95% CI, 29.2%-100%) and 75% (95% CI, 19.4%-99.4%), respectively. CONCLUSIONS: All 3 diagnostic tests are highly specific, and a positive test result is highly predictive of disease presence. IVCM is both highly sensitive and specific when performed by an experienced operator. PCR is a useful adjunct in the diagnosis of AK because of its wider availability compared with IVCM, and it may be used in combination with IVCM for microbiologic confirmation.

Long-Term Outcomes of High-Risk Keratoplasty in Patients Receiving Systemic Immunosuppression.

PURPOSE: Immunological graft rejection after corneal transplantation remains the leading cause of graft failure. Systemic immunosuppression is used for keratoplasty at a high risk of rejection to improve graft survival. We examined the long-term outcomes of high-risk corneal grafts in patients receiving systemic immunosuppression. METHODS: Thirty-five corneal transplants with a high risk of rejection were identified from 29 patients within a regional immunosuppression service in the United Kingdom. Definition of keratoplasty at "high risk" of rejection included one or more of the following: a history of ipsilateral graft rejection and/or failure, 2 or more quadrants of stromal vascularization, perforation or ocular inflammation at the time of surgery, presence of atopy, and a large-diameter (≥9 mm) graft. Median follow-up duration was 5 years after transplantation. RESULTS: Graft survival at 5 years in patients receiving systemic immunosuppression was 73.5%. Rejection episodes occurred in 14 grafts (40%); these episodes were reversible in 10 grafts (71%). Indications for transplantation were mostly visual (n = 19; 54%) and tectonic (n = 14; 40%). Eighteen grafts (51%) had 2 or more high-risk characteristics. Most patients (n = 20; 69%) received monotherapy, commonly with tacrolimus (n = 15; 52%) or mycophenolate mofetil (n = 8; 28%). Three patients (10%) experienced severe systemic side effects. Median "day-to-day" logMAR visual acuity was 0.5 in grafts for all indications and 0.2 for visual indications. CONCLUSIONS: Systemic immunosuppression in patients with high-risk keratoplasty seems to improve graft survival with a median follow-up duration of 5 years and is tolerated by most patients. Despite rejection episodes occurring in 40% of grafts, these were mostly reversible.