VERTICAL AND HORIZONTAL METAMORPHOPSIA ONE YEAR AFTER SURGERY FOR MACULAR HOLES ≤ 500 µ m WITH AND WITHOUT INVERTED INTERNAL LIMITING MEMBRANE FLAP.

PURPOSE: To investigate the effect of an inverted internal limiting membrane flap (IF) and other factors on metamorphopsia after macular hole surgery. METHODS: Prospective case series of patients undergoing pars plana vitrectomy with gas tamponade, with either conventional internal limiting membrane peeling (CP) or an IF, for primary idiopathic macular holes ≤ 500 µ m. Vertical and horizontal metamorphopsia were measured as M-scores (degrees) using M-charts preoperatively and at 2, 6, and 12 months postoperatively. RESULTS: Fifty-three eyes of 53 patients were included of whom 27 underwent CP and 26 were treated with an IF. After macular hole surgery, all patients were pseudophakic. Vertical and horizontal metamorphopsia improved from 1.08 (±0.51) and 0.98 (±0.70) preoperatively to 0.58 (±0.37) and 0.45 (±0.36) at 2 months ( P < 0.01), with no further significant improvement at 6 months (0.39 [±0.31], P = 0.07 and 0.31 [±0.28], P = 0.18) or at 12 months (0.37 [±0.30], P = 0.72 and 0.28 [±0.28], P = 0.99). There was no significant difference in the mean vertical and horizontal metamorphopsia between patients with CP and with an IF at 2 months ( P = 0.063, P = 0.10), 6 months ( P = 0.25, P = 0.16), or 12 months ( P = 0.62, P = 0.22). Preoperative vertical M-score improved at 12 months after macular hole surgery by 61% and 64% in the CP and IF groups, respectively ( P = 0.84), and the horizontal M-score by 65% and 71%, respectively ( P = 0.98). CONCLUSION: The use of an IF has no evident bearing on the degree of postoperative metamorphopsia 12 months after surgical repair of macular holes ≤ 500 µ m.

OPTICAL COHERENCE TOMOGRAPHY FEATURES ASSOCIATED WITH VITREOMACULAR TRACTION RELEASE AND MACULAR HOLE SIZE PROGRESSION FOLLOWING TREATMENT WITH OCRIPLASMIN.

PURPOSE: To evaluate OCT features for vitreomacular traction (VMT) release and change in macular hole (MH) size after treatment with ocriplasmin. METHODS: Patients who had undergone treatment with ocriplasmin for VMT with or without MH ≤400 µm were included. The main outcomes were VMT release and changes in minimum linear diameter MH size at 4 weeks in MHs that persisted. OCT features evaluated were central retinal thickness, vitreomacular adhesion length, posterior vitreous cortex (PVC) insertion angles 500 µm from the insertion points, and minimum linear diameter size. RESULTS: Sixty patients were included: 37 had isolated VMT and 23 VMT with a MH. Four weeks after ocriplasmin injection, the overall VMT release rate was 66.7% (40/60); 64.9% (24/37) in eyes with isolated VMT and 69.6% (16/23) in eyes with MH. VMT release was associated with younger age (P = 0.02). Macular hole closure was achieved in 26.1% (6/23) and was associated with a smaller ratio of the temporal to the nasal PVC angle (P < 0.01). Of the 17 persistent MHs, 76.5% (13/17) increased in minimum linear diameter size from baseline 186 (±78) to 358 (±133) µm (P < 0.001). Progression in minimum linear diameter size showed a negative linear association with the size of the nasal PVC angle (R2 = 0.39, P = 0.002) and a positive linear association with the ratio of the temporal to nasal PVC angle (R2 = 0.39, P = 0.002). CONCLUSION: In patients with VMT-associated MHs, the risk of MH enlargement following ocriplasmin is negatively correlated with the nasal PVC angle size and is increased if the ratio of the temporal to nasal angle is >1.

INFLUENCE OF PREOPERATIVE POSTURING ON SUBFOVEAL FLUID HEIGHT IN MACULA-OFF RETINAL DETACHMENTS.

PURPOSE: To evaluate the effect of preoperative posturing on subfoveal fluid height (SFFH) in macula-off retinal detachment. METHODS: A prospective study including patients with macula-off retinal detachment with SFFH measurable on optical coherence tomography (OCT) and duration of loss of central vision (LCV) ≤ 7 days. Linear OCT volume scans were performed at baseline, after 1 minute, 1 hour, 4 hours, and on the next morning. For the first hour, all patients remained in an upright position. Patients were then either instructed to posture until the surgery according to the location of the primary retinal break (posturing group) or were not given any instructions (control group). RESULTS: Twenty-four patients were included in the posturing group and 11 patients in the control group. There was no significant change in SFFH between baseline, 1 minute, 1 hour, and 4 hours. The mean SFFH in the control group increased by 243 µ m from 624 (±268) µ m at baseline to 867 (±303) µ m the next morning ( P < 0.01) but decreased in the posturing group by 150 µ m from 728 (±416) to 578 (±445) µ m ( P = 0.03). There was a significant association of the SFFH the next morning with posturing ( P < 0.01) and SFFH at baseline ( P < 0.01), but not with location of primary break ( P = 0.20). The change in SFFH from baseline to the next morning was significantly associated with posturing and primary break location ( P < 0.01), but not with SFFH at baseline ( P = 0.21). CONCLUSION: Preoperative posturing is an effective measure to prevent progression of macular detachment in macula-off retinal detachment.

Impact of fluoroquinolones and aminoglycosides on P. aeruginosa virulence factor production and cytotoxicity.

The opportunistic pathogen Pseudomonas aeruginosa is one of leading causes of disability and mortality worldwide and the world health organisation has listed it with the highest priority for the need of new antimicrobial therapies. P. aeruginosa strains responsible for the poorest clinical outcomes express either ExoS or ExoU, which are injected into target host cells via the type III secretion system (T3SS). ExoS is a bifunctional cytotoxin that promotes intracellular survival of invasive P. aeruginosa by preventing targeting of the bacteria to acidified intracellular compartments. ExoU is a phospholipase which causes destruction of host cell plasma membranes, leading to acute tissue damage and bacterial dissemination. Fluoroquinolones are usually employed as a first line of therapy as they have been shown to be more active against P. aeruginosa in vitrothan other antimicrobial classes. Their overuse over the past decade, however, has resulted in the emergence of antibiotic resistance. In certain clinical situations, aminoglycosides have been shown to be more effective then fluoroquinolones, despite their reduced potency towards P. aeruginosa in vitro. In this study, we evaluated the effects of fluoroquinolones (moxifloxacin and ciprofloxacin) and aminoglycosides (tobramycin and gentamycin) on T3SS expression and toxicity, in corneal epithelial cell infection models. We discovered that tobramycin disrupted T3SS expression and reduced both ExoS and ExoU mediated cytotoxicity, protecting infected HCE-t cells at concentrations below the minimal inhibitory concentration (MIC). The fluoroquinolones moxifloxacin and ciprofloxacin, however, up-regulated the T3SS and did not inhibit and may have increased the cytotoxic effects of ExoS and ExoU.

Anatomical and functional outcomes of pneumatic vitreolysis for treatment of vitreomacular traction with and without macular holes.

PURPOSE: To evaluate the outcome of pneumatic vitreolysis (PVL) for vitreomacular traction (VMT) with or without full thickness macular hole (MH) < 400 µm. METHODS: Forty-seven eyes of 47 patients were included who had undergone PVL for VMT with or without MH. Main outcome measures were release of VMT, MH closure, best-corrected visual acuity (BCVA) and adverse events. RESULTS: Thirty-three patients had isolated VMT and 14 patients VMT with a MH. Four weeks after PVL, the overall VMT release rate was 35/47 (74.5%): 25/37 (67.6%) in phakic and 10/10 (100%) in pseudophakic eyes (p = 0.03). Four of 14 MH (28.6%) were closed. Twenty-two of 47 (46.8%) eyes required a subsequent PPV: 12/33 (36.4%) in the VMT only group and 10/14 (71.4%) in the VMT with MH group. Mean BCVA improved from 0.48 (± 0.24) to 0.34 (± 0.23) logMAR at 6 months in patients with VMT alone (p < 0.001), and from 0.57 (± 0.27) to 0.41 (± 0.28) logMAR in patients with VMT and MH (p = 0.008). Adverse events included new formation of a large MH in 4/33 (12.1%) eyes, failure of MH closure in 10/14 (71.4%) eyes, progression of mean minimum linear diameter (MLD) MH size from baseline 139 (± 67) to 396 (± 130) µm (p < 0.001) and development of a retinal detachment in 4/47 (8.5%) eyes. CONCLUSION: While PVL leads to a high VMT release rate particularly in pseudophakic eyes, it is associated with a relatively high incidence of MH formation, MH size progression and retinal detachment.

A pipeline to evaluate inhibitors of the Pseudomonas aeruginosa exotoxin U.

Pseudomonas aeruginosa has recently been highlighted by the World Health Organisation (WHO) as a major threat with high priority for the development of new therapies. In severe P. aeruginosa infections, the phospholipase activity of the type 3 secretion system toxin, ExoU, induces lysis of target host cells and results in the poorest clinical outcomes. We have developed an integrated pipeline to evaluate small molecule inhibitors of ExoU in vitro and in cultured cell models, including a disease-relevant corneal epithelial (HCE-T) scratch and infection model using florescence microscopy and cell viability assays. Compounds Pseudolipasin A, compound A and compound B were effective in vitro inhibitors of ExoU and mitigated P. aeruginosa ExoU-dependent cytotoxicity after infection of HCE-T cells at concentrations as low as 0.5 µM. Addition of the antimicrobial moxifloxacin controlled bacterial load, allowing these assays to be extended from 6 h to 24 h. P. aeruginosa remained cytotoxic to HCE-T cells with moxifloxacin, present at the minimal inhibitory concentration for 24 h, but, when used in combination with either Pseudolipasin A, compound A or compound B, a greater amount of viable cells and scratch healing were observed. Thus, our pipeline provides evidence that ExoU inhibitors could be used in combination with certain antimicrobials as a novel means to treat infections due to ExoU producing P. aeruginosa, as well as the means to identify more potent ExoU inhibitors for future therapeutics.

Epithelial Cell-Derived Extracellular Vesicles Trigger the Differentiation of Two Epithelial Cell Lines.

Extracellular vesicles (EVs), specifically exosomes, carry a cell-type dependent cargo that is transported to the recipient cell and translated in the presence of a required machinery. Differences in the cargo carried by the corneal and conjunctival-derived EVs could be the agent that triggers the transdifferentiation of these two cell populations. Therefore, this study investigates the role of EVs in triggering the plasticity of corneal and conjunctival epithelial cells and identifies prospective miRNA and genes responsible for maintaining ocular surface homeostasis. The EVs were extracted from the conditioned media (after starving) of corneal epithelial (hTCEpi) and conjunctival (HCjE-Gi) cell lines using ultracentrifugation. HCjE-Gi cells were cultured with hTCEpi-derived EVs and vice-versa. The EVs were characterized as exosomes using Nanosight and Flow cytometry. KRT3 and KRT12 were used as associated corneal markers, whereas KRT7 and KRT13 were used as associated conjunctival markers with ΔNp63 as a differentiation marker. Shift of these markers was an indication of transdifferentiation. The cargo of the extracted exosomes from both the cell types was explored using next-generation sequencing. The hTCEpi-derived EVs induced conjunctival epithelial cells to express the corneal-associated markers KRT3 and KRT12, losing their conjunctival phenotype at both the mRNA and protein level. Simultaneously, HCjE-Gi-derived EVs induced corneal epithelial cells to express the conjunctival associated markers KRT7 and KRT13, losing their corneal phenotype. This process of differentiation was accompanied by an intermediate step of cell de-differentiation showed by up-regulation in the expression of epithelial stem cell marker ΔNp63, also shown on the ex vivo human cadaveric donor corneas. miRNA molecules (total of 11 including precursor and mature) with significant differences in their relative abundance between the two populations (p < 0.05) were found and investigated. miR-9-5p expression was higher in HCjE-Gi cells and HCjE-Gi-derived EVs when compared to hTCEpi cells and hTCEPi-derived EVs (p < 0.001). The results suggest that EVs released by the two cell types have the ability to influence the transdifferentiation of human conjunctival and corneal epithelial cells. miR-9-5p could have a role in stem cell homeostasis and cell differentiation via HES-1 gene.

FUNCTIONAL AND MORPHOLOGICAL OUTCOMES OF THE INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE IN SMALL-SIZED AND MEDIUM-SIZED MACULAR HOLES <400 µm.

PURPOSE: To assess the effect of an internal limiting membrane flap (IF) in macular hole surgery on the best-corrected visual acuity (BCVA) and integrity of the ellipsoid zone (EZ) and external limiting membrane. METHODS: Patients were included who had successful surgery for macular hole <400 µm with or without an IF. Main outcome measures were BCVA and restoration of the external limiting membrane and EZ at 12 months. RESULTS: Sixty patients were included, 36 with conventional peeling and 24 with an IF. The best-corrected visual acuity improved from 0.74 (±0.30) logarithm of the minimum angle of resolution (20/110 Snellen) to 0.26 (±0.20) (20/36 Snellen) in patients without and from 0.77 (±0.32) logarithm of the minimum angle of resolution (20/118 Snellen) to 0.18 (±0.12) (20/30 Snellen) in patients with an IF, respectively. There was no difference in the integrity of the EZ and external limiting membrane in patients with or without an IF at either 3 (P = 0.58, P = 0.20), 6 (P = 0.81, P = 0.10), or 12 months (P = 0.60, P = 0.20) or in the BCVA at 3 (P = 0.24), 6 (P = 0.18) and 12 months (P = 0.11). In the multivariable model, only preoperative BCVA (P < 0.01), EZ integrity (P = 0.001), and age (P < 0.01) were associated with the post-operative BCVA. CONCLUSION: In patients undergoing surgery for macular hole <400 µm, the use of an IF did not affect the BCVA or the integrity of the EZ and external limiting membrane.

Cost analysis of eye bank versus surgeon prepared endothelial grafts.

BACKGROUND: Selective lamellar corneal transplantation (keratoplasty) has overtaken full thickness penetrating keratoplasty as the graft choice for endothelial failure. Even more recently eye bank prepared tissues are becoming increasing popular as a way to reduce the risks of tissue loss and stress during endothelial keratoplasty preparation in the surgical theatre. This study compares costs between surgeon and eye bank prepared tissues for Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet's membrane endothelial keratoplasty (DMEK). METHODS: Retrospective study conducted at the Royal Liverpool University Hospital including endothelial keratoplasties with a minimum of 6 months follow-up time. Cost analysis included surgical expenses, tissue acquisition fees, cost of patient's ward admission and out-patient expenses, including cost of re-bubbling procedures, costs of visits, anterior segment imaging and optometrist visits within the first 6 months follow-up. RESULTS: Ninety-eight eyes of 98 patients were included in the study of which 42 underwent DSAEK surgery and 56 DMEK surgery. Cost analysis of surgical expenses in the DSAEK group showed a significant difference between using surgeon prepared and eye bank prepared tissue (£3866 ± 296 and £4389 ± 360, respectively; p < 0.01) and the same was found in the DMEK group (£3682 ± 167 and £4162 ± 167 for surgeon prepared and eye bank prepared tissues, respectively; p < 0.01). Cost of out-patient visits did not differ significantly in either group. CONCLUSIONS: At the Royal Liverpool University Hospital, eye bank prepared tissues had higher surgical expenses compared to those prepared by the surgeon, while the post-operative care expenses were similar between the two groups.

En-face analysis of the human limbal lymphatic vasculature.

PURPOSE: To describe the location and morphometric characteristics of the human limbal lymphatic vasculature and its relation to the marginal corneal vascular arcades (MCA). METHODS: Ex vivo confocal microscopic (CM) imaging and immunofluorescence double staining for CD-31 and D2-40 of histological en-face sections using 12 preserved human cadaveric corneoscleral discs were performed, followed by a semi-automated morphometric analysis of the two-dimensional vascular network architecture. RESULTS: Ex vivo CM confirmed the presence of 2 distinct vascular networks. The haematic limbal vascular complex (HLVC) extended further into the cornea, forming typical MCAs. The lymphatic limbal vascular complex (LLVC) was peripheral from the termination of Bowman's layer and was also found to be peripheral to and deeper than the HLVC. LLVC and HLVC were significantly different with respect to vessel diameter, segment length and wall thickness. CONCLUSION: The lymphatic vasculature of the human corneoscleral limbal region displays specific morphometric features that allow its differentiation from haematic vessels using CM.

Outcome of Descemet stripping automated endothelial keratoplasty in eyes with an Ahmed glaucoma valve.

PURPOSE: The purpose was to investigate the survival of Descemet stripping automated endothelial keratoplasty (DSAEK) in eyes with an Ahmed glaucoma valve (AGV). METHODS: The study had a retrospective case-series of patients with an AGV in the anterior chamber undergoing a DSAEK. Included in the analysis were graft size, number of previous operations, post-operative glaucoma medications, post-operative intraocular pressure (IOP) control, graft size and donor factors (age, endothelial cell density, and post-mortem time). A generalised linear model with binary logistic regression was used to test for an effect on graft survival at 1 year and 1.5 years. RESULTS: Fourteen eyes from 13 patients were included. The survival rate of the first DSAEK at 6, 12, 18, 24 and 30-months was 85%, 71%, 50%, 36% and 30%, respectively. The mean duration to graft failure was 12.9 ± 6.2 months. Five of the seven failed first grafts went on to have a repeat DSAEK. The mean follow-up in this subgroup was 30.7 ± 18.4 months. The survival rate of second DSAEK at 6, 12, 18 and 24 months was 100% (5/5), 100% (5/5), 75% (3/4) and 67% (2/3). Only one second DSAEK failed in the duration of the study and went on to receive a third DSAEK which failed at 18-months. The mean IOP within the first year was significantly lower for grafts that survived at 1 and 1.5 years (17.4 mmHg, 16.9 mmHg) than for grafts that failed (19.4 mmHg, 19.4 mmHg) (p = 0.04, p = 0.009). CONCLUSION: DSAEK is a viable alternative to PK to restore visual function in eyes with an AGV sited in the anterior chamber. IOP is an important risk factor for graft failure.

Intraoperative management of macroperforations of Descemet's membrane in deep anterior lamellar keratoplasty.

BACKGROUND: To describe a surgical approach for the completion of pre-descemetic deep anterior lamellar keratoplasty (pdDALK) in the presence of a macroperforation of Descemet's membrane (DM). METHODS: Using case notes, we recorded the details of the intra- and perioperative course of patients who underwent successful pdDALK in the presence of macroperforation. A literature search of pdDALK techniques available to the corneal surgeon in a similar scenario was undertaken. RESULTS: In two very different scenarios with intra- or preoperative perforation of DM, a centripetal layered lamellar dissection was performed and allowed completion of pdDALK with a residual recipient central stromal thickness of 36 and 115 µm and good visual outcome. CONCLUSION: Despite very different scenarios, a centripetal layered lamellar dissection offers an approach for the completion of pdDALK in the presence of a macroperforation.

Endophthalmitis after penetrating keratoplasty.

PURPOSE: To determine the incidence of endophthalmitis after penetrating keratoplasty (PK) and patient and donor risk factors. DESIGN: Retrospective cohort study using national transplant registry data. PARTICIPANTS: All corneal transplant recipients (n = 11 320) registered on the United Kingdom Transplant Registry undergoing their first PK between April 1999 and December 2006. METHODS: Patients who developed endophthalmitis were identified on the transplant registry. In addition, cases where the fellow cornea from the same donor had been transplanted were included. Clinical information regarding donor and recipient characteristics, surgical details, and postoperative outcomes were collected and analyzed. In cases where endophthalmitis was reported, the diagnosis was verified by a follow-up supplementary questionnaire to the surgeon. Logistic regression was used to investigate differences in the factors associated with the development of endophthalmitis. MAIN OUTCOME MEASURES: Incidence of endophthalmitis and graft survival. RESULTS: The overall incidence of endophthalmitis occurring after primary PK in the UK was 0.67%. The incidence of endophthalmitis occurring within 6 weeks of surgery was 0.16%. Graft survival after endophthalmitis was 27% (95% confidence interval, 16-38) at 5 years, with a mean best-corrected visual acuity of 1.13 (logarithm of the minimum angle of resolution) for surviving grafts. Factors associated with endophthalmitis were donor cause of death (infection), high-risk cases, and indication for corneal transplantation. CONCLUSION: Endophthalmitis remains a serious issue, with those affected having reduced graft survival and poor visual outcomes. Management of the identified recipient and donor risk factors are important to reduce endophthalmitis risk. In particular, the increased incidence of endophthalmitis when the donor dies of infection requires further explanation and review of current donor eye retrieval and eye bank practices. The delayed presentation of endophthalmitis cases also raises questions regarding possible sequestration of microbes within the corneal tissue and the effect of antimicrobials in storage media.

Corneal angiography for guiding and evaluating fine-needle diathermy treatment of corneal neovascularization.

PURPOSE: To investigate the outcome of selective occlusion of the afferent vessel of corneal neovascular complexes (CoNVs), using angiographically guided fine-needle diathermy (FND). DESIGN: Retrospective interventional case series. SUBJECTS: Patients with CoNV unresponsive to topical steroid therapy. METHODS: Visual acuity, color images, and fluorescein angiography and indocyanine green angiography were measured before and after FND with a minimum of 3 months of follow-up. The number of afferent vessels crossing the limbus, time to fluorescein leakage, area, and geometric properties of the CoNV were determined using an in-house automated program written in numerical computing language (MatLab R14; The MathWorks Inc., Natick, MA). The location of the afferent vessel was identified from the angiographic images and marked at the slit lamp using a needle to make a cut to the depth of the vessel. We then applied FND using an electrolysis needle. MAIN OUTCOME MEASURES: Area of CoNV. RESULTS: Thirty patients underwent FND for CoNV that had not responded to treatment with topical steroids. The CoNV was associated with previous microbial keratitis (n = 26), intrastromal corneal ring segments (n = 2), ectodermal dysplasia (n = 1), and corneal choristoma (n = 1). Duration of CoNV was >6 months in 23 patients (77%), between 3 and 6 months in 3 patients (10%), and <3 months in 5 patients (13%). The number of afferent vessels per CoNV ranged from 1 to 3, with a mean diameter of 40 µm (standard deviation [SD], 10 µm) and mean time to leakage from apical vessels was 44.22 seconds (minimum, 27.43 seconds; maximum, 63.59 seconds). The number of FND treatments that were required was 1 for 20 patients (66.6%), 2 for 8 patients (26.6%), and 3 for 2 patients (6.6%). After FND, the area of CoNV reduced by 1.80 mm(2) (SD, 1.40 mm(2)), from 2.42 (SD, 1.59) to 0.62 mm(2) (SD, 0.73 mm(2)) up to 12 weeks postoperatively (P < 0.01). CONCLUSIONS: The differentiation of afferent and efferent vessels using corneal angiography enables treatment to be selectively applied to the afferent vessels; there are usually 1 to 2 for each CoNV complex.

Common and new acyclovir resistant herpes simplex virus-1 mutants causing bilateral recurrent herpetic keratitis in an immunocompetent patient.

We investigated thymidine kinase (tk) mutants isolated during multiple episodes of recurrent bilateral acyclovir resistant herpes simplex keratitis in an immunocompetent patient. From one eye, we found a single guanine insertion, previously shown to greatly reduce TK expression, and from the other, a previously unidentified substitution, which genetic experiments confirmed confers drug resistance. The substitution, although distant from substrate binding sites, reduced thymidine phosphorylation 10-20-fold, and acyclovir phosphorylation >100-fold. This phenotype should permit reactivation from latency to cause recurrent disease. The results may have implications for the prevalence and prevention of acyclovir resistance in patients with herpes simplex keratitis.

Ocular phenotype and therapeutic interventions in keratitis-ichthyosis-deafness (KID) syndrome.

BACKGROUND: To report ocular manifestations, clinical course, and therapeutic management of patients with molecular genetically confirmed keratitis-ichthyosis-deafness syndrome. METHODS: Four patients, aged 19 to 46, with keratitis-ichthyosis-deafness syndrome from across the UK were recruited for a general and ocular examination and GJB2 (Cx26) mutational analysis. The ocular examination included best-corrected visual acuity, slit-lamp bio-microscopy, and ocular surface assessment. Mutational analysis of the coding region of GJB2 (Cx26) was performed by bidirectional Sanger sequencing. RESULTS: All four individuals had the characteristic systemic features of keratitis-ichthyosis-deafness syndrome. Each patient was found to have a missense mutation, resulting in the substitution of aspartic acid with asparagine at codon 50 (p.D50N). Main ophthalmic features were vascularizing keratopathy, ocular surface disease, hyperkeratotic lid lesions, recurrent epithelial defects, and corneal stromal scarring. One patient had multiple surgical procedures, including superficial keratectomies and lamellar keratoplasty, which failed to prevent severe visual loss. In contrast, oral therapy with ketoconazole stabilized the corneal and skin disease in two other patients with keratitis-ichthyosis-deafness syndrome. The patient who underwent intracorneal bevacizumab injection showed a marked reduction in corneal vascularization following a single application. CONCLUSIONS: Keratitis-ichthyosis-deafness syndrome is a rare ectodermal dysplasia caused by heterozygous mutations in GJB2 (Cx26) with a severe, progressive vascularizing keratopathy. Oral ketoconazole therapy may offer benefit in stabilizing the corneal and skin disease.

Microbial keratitis in Southern Malawi: a microbiological pilot study.

OBJECTIVE: Microbial keratitis (MK) is a significant cause of blindness in sub-Saharan Africa. We investigated the feasibility of using a novel corneal impression membrane (CIM) for obtaining and processing samples by culture, PCR and whole-genome sequencing (WGS) in patients presenting with suspected MK in Malawi. METHODS AND ANALYSIS: Samples were collected from patients presenting with suspected MK using a 12 mm diameter polytetrafluoroethylene CIM disc. Samples were processed using culture and PCR for Acanthamoeba, herpes simplex virus type 1 (HSV-1) and the bacterial 16S rRNA gene. Minimum inhibitory concentrations of isolates to eight antimicrobials were measured using susceptibility strips. WGS was used to characterise Staphylococcus aureus isolates. RESULTS: 71 eyes of 71 patients were included. The overall CIM isolation rate was 81.7% (58 positive samples from 71 participants). 69 (81.2%) of isolates were Gram-positive cocci. Coagulase-negative Staphylococcus 31.8% and Streptococcus species 14.1% were the most isolated bacteria. Seven (9.9%) participants were positive for HSV-1. Fungi and Acanthamoeba were not detected. Moxifloxacin and chloramphenicol offered the best coverage for both Gram-positive and Gram-negative isolates when susceptibility was determined using known antimicrobial first quartile concentrations and European Committee on Antimicrobial Susceptibility Testing breakpoints, respectively. WGS identified known virulence genes associated with S. aureus keratitis. CONCLUSIONS: In a resource-poor setting, a CIM can be used to safely sample the cornea in patients presenting with suspected MK, enabling identification of causative microorganisms by culture and PCR. Although the microbiological spectrum found was limited to the dry season, these preliminary results could be used to guide empirical treatment.

Preoperative Posterior Stromal Ripples as Predictive Biomarkers of Visual Recovery After DMEK.

PURPOSE: To investigate the role of preoperative posterior stromal ripples (pre-PSR) on visual acuity recovery after Descemet membrane endothelial keratoplasty (DMEK). METHODS: This is a comparative case series retrospectively analyzing patients who underwent DMEK. Electronic records and imaging of DMEK patients were reviewed. The last preoperative and first postoperative available anterior segment optical coherence tomography scans for each eye were analyzed for the presence of pre-PSR. The difference in longitudinal trends of visual acuity recovery after DMEK was assessed in eyes with and without pre-PSR. The frequency of rebubbling and measures of proportional relative risk of rebubbling were analyzed according to the presence of preoperative and postoperative PSR. RESULTS: A total of 66 patients (71 eyes) were included. Pre-PSR were associated with lower preoperative visual acuity [0.6 (0.5) vs. 0.9 (0.6) LogMAR, P = 0.02] and higher central corneal thickness [613 (73.8) vs. 715.7 (129.6) micron, P < 0.001]. Eyes with pre-PSR had a slower visual recovery up to 3.5 months after surgery compared to eyes without pre-PSR and achieved lower final visual acuity [0.1 (0.2) vs. 0.3 (0.3) LogMAR, P = 0.02]. Cox proportional hazard ratios showed that postoperative PSR were associated with a greater risk of rebubbling [hazard ratio (95% CI), 7.1 (1.3, 39.5), P = 0.02] while pre-PSR were not. CONCLUSIONS: The presence of pre-PSR is associated with slower visual recovery and lower final visual acuity after DMEK while postoperative PSR confer a higher risk of rebubbling. PSR represent a valuable prognostic biomarker both before and after DMEK.

The effect of socioeconomic deprivation on corneal graft survival in the United Kingdom.

OBJECTIVE: To investigate the effect of socioeconomic deprivation on cornea graft survival in the United Kingdom. DESIGN: Retrospective cohort study. PARTICIPANTS: All the recipients (n = 13,644) undergoing their first penetrating keratoplasty (PK) registered on the United Kingdom Transplant Registry between April 1999 and March 2011 were included. METHODS: Data of patients' demographic details, indications, graft size, corneal vascularization, surgical complication, rejection episodes, and postoperative medication were collected at the time of surgery and 1, 2, and 5 years postoperatively. Patients with endophthalmitis were excluded from the study. Patients' home postcodes were used to determine the socioeconomic status using a well-validated deprivation index in the United Kingdom: A Classification of Residential Neighborhoods (ACORN). Kaplan-Meier survival and Cox proportional hazards regression were used to evaluate the influence of ACORN categories on 5-year graft survival, and the Bonferroni method was used to adjust for multiple comparisons. MAIN OUTCOME MEASURES: Patients' socioeconomic deprivation status and corneal graft failure. RESULTS: A total of 13,644 patients received their first PK during the study periods. A total of 1685 patients (13.36%) were lost to follow-up, leaving 11,821 patients (86.64%) for analysis. A total of 138 of the 11,821 patients (1.17%) developed endophthalmitis. The risk of graft failure within 5 years for the patients classified as hard-pressed was 1.3 times that of the least deprived (hazard ratio, 1.3; 95% confidence interval, 1.1-1.5; P = 0.003) after adjusting for confounding factors and indications. There were no statistically significant differences between the causes of graft failure and the level of deprivation (P = 0.14). CONCLUSIONS: Patients classified as hard-pressed had an increased risk of graft failure within 5 years compared with the least deprived patients.