Integration and remodelling of a collagen anterior lamellar keratoplasty graft in an animal model - A preliminary report.

There is an international shortage of donor corneas for transplantation to treat the 1.5-2.0 million new cases of blindness secondary to corneal disease. Research has therefore been directed towards the development of artificial corneas using alternative materials such as collagen. The biocompatibility of an acellular collagen-based scaffold for anterior lamellar keratoplasty was investigated in vivo in a rabbit model. This scaffold has previously shown promise as a corneal substitute in vitro. Slit-lamp and Optical Coherence Tomography examinations were carried out at 2 weeks, 1, 2, 3, and 6 months post-operatively. Graft-host integration was investigated using immunohistochemistry of the cornea at 6 months. Results showed that the graft was biocompatible, supported corneal re-epithelialisation, and showed no signs of rejection. Migration of stromal cells into areas of the graft was observed, however this was accompanied by extensive graft digestion. Whilst the scaffold was biocompatible, further modifications to the material or supplementation with matrix metalloproteinase inhibitors are required to bring us closer to a stable and fully integrated corneal substitute.

Five-year results of a prospective, randomised, contralateral eye trial of corneal crosslinking for keratoconus.

BACKGROUND: Few studies have evaluated corneal crosslinking (CXL) in a prospective, randomised fashion. This study aimed to determine the efficacy and safety of CXL to reduce the progression of keratoconus. METHODS: Prospective, unmasked, randomised, contralateral eye controlled trial at a tertiary eye centre. PARTICIPANTS: Individuals with bilateral progressive keratoconus. One eye from each subject was randomised to CXL and the contralateral, untreated eye acted as the control. PRIMARY OUTCOME MEASURE: change in maximum keratometry. SECONDARY OUTCOME MEASURES: uncorrected distance visual acuity, spectacle corrected distance visual acuity, spherical equivalent refraction, simulated keratometry, corneal astigmatism, minimum pachymetry and complications. RESULTS: Thirty-eight individuals (mean age 21.1 ± 6.7 years) were enrolled with one eye treated with CXL. At 5 years, there was a mean decrease in maximum keratometry of treated eyes (-1.45 ± 2.25 D) compared to an increase among the controls (1.71 ± 2.46 D; p < 0.001). There were significant differences between the treated and control groups in the mean change of Steep SimK (-1.07 ± 1.22 vs. 0.96 ± 1.97 D; p < 0.001), Flat SimK (-0.61 ± 1.34 vs. 0.43 ± 1.12 D; p < 0.001), corneal astigmatism (-0.45 ± 1.31 vs. 0.63 ± 1.52 D; p < 0.01) and minimum pachymetry (-32.49 ± 26.32 vs. -13.57 ± 24.11 µm; p < 0.01). Complications included sterile infiltrates (n = 2), microbial keratitis (n = 1), persistent corneal haze/scarring at 5 years (n = 4) and loss of ≥2 lines of corrected distance visual acuity (n = 3). CONCLUSIONS: CXL is an effective and relatively safe intervention to halt or reduce the progression of keratoconus in the majority of eyes for at least 5 years.

Successful culture of human transition zone cells.

BACKGROUND: Human corneal endothelial cells undergo very little or no proliferation and respond to cell loss by migration and cellular enlargement. Significant cell loss or damage may result in corneal oedema, opacity and loss of vision. In vitro expansion of corneal endothelial cells (CECs) is a promising strategy for corneal regeneration. The transition zone (TZ) may be an alternative source of CECs. The objective of this study was to establish a protocol for TZ cell culture, and to determine their potential to proliferate and differentiate into cells that resemble CECs in vitro. METHODS: An explant culture protocol for the human TZ was established. Cell proliferation was assessed using 5-ethynyl-2'-deoxyuridine (EdU) assay. The expression of stem cell and endothelial markers was assessed using immunohistochemistry and quantitative polymerase chain reaction. RESULTS: TZ cells can be passaged up to 12 times; cells became polygonal 3 to 4 passages before senescence. An average of 41% of cells incorporated EdU over a 5-day period. TZ cells expressed the corneal endothelial proteins ZO-1 and Na+ /K+ ATPase, Col8A2, the periocular mesenchyme marker PITX2, and the neural crest stem cell markers Nestin and Sox10. TZ cells expressed mRNA of a range of neural crest, periocular mesenchyme, and corneal endothelial genes. CONCLUSIONS: TZ cells can proliferate and differentiate into cells that resemble CECs, demonstrating their potential to be an alternative cell source for corneal endothelial cell therapy.

Topographic screening reveals keratoconus to be extremely common in Down syndrome.

IMPORTANCE: Keratoconus disproportionately affects people with Down syndrome (DS). This is the first study of its kind in Australasia. BACKGROUND: To investigate the prevalence of keratoconus in DS. DESIGN: Cross-sectional study. PARTICIPANTS: Athletes with DS attending 2017 New Zealand Special Olympics National Summer Games. METHODS: Keratoconus was identified using corneal topography (TMS-4N, Tomey). Topography from both eyes was required to be included. Two independent quantitative criteria were used to indicate keratoconus. The first was keratoconus severity index ≥ 30%. The second, adapted from the literature, required at least four of eight topographic parameters to be abnormal. Data from the worse eye were analysed. Diagnosis in each group was subsequently confirmed qualitatively by three corneal fellowship-trained ophthalmologists. Those with a definitive diagnosis were grouped into Keratoconus Confirmed Group 1 (KCC1) and Keratoconus Confirmed Group 2 (KCC2), respectively. MAIN OUTCOME MEASURES: Keratoconus prevalence, severity, demographics. RESULTS: Of 110 athletes screened, N = 98 were included, mean age 30.0 ± 9.7 years. Using only topographic data, keratoconus was identified in 39 (39.8%) athletes by quantitative topographic criteria 1, and in 63 (64.3%) athletes by criteria 2. Keratoconus was confirmed by qualitative sub-specialist review in 30 (30.6%) (KCC1) and 38 (38.8%) (KCC2) athletes, respectively. Mean keratometry in groups KCC1 and KCC2 were 48.4 ± 3.2D and 48.2 ± 2.9D, respectively. Most were male (KCC1 63.3%, KCC2 76.3%) and of European ethnicity (KCC1 80%, KCC2 78.9%). CONCLUSIONS AND RELEVANCE: We report keratoconus in 30.6% to 38.8% of athletes with DS; therefore, we believe keratoconus screening is indicated in DS for early management.

Auckland Cataract Study IV: Practical application of NZCRS cataract risk stratification to reduce phacoemulsification complications.

IMPORTANCE: Reduction of intraoperative complications in phacoemulsification cataract surgery. BACKGROUND: To assess practicability of a risk stratification system, the New Zealand Cataract Risk Stratification (NZCRS) system, in a major teaching hospital service, without investigator oversight, to ascertain whether benefits identified in research studies are maintained in busy clinical practice. DESIGN: Prospective cohort study in a major public teaching hospital. PARTICIPANTS: Five hundred cases of phacoemulsification cataract surgery. METHODS: NZCRS system inserted into 621 consecutive preoperative cataract patient files. Recommendation to allocate higher-risk cases to experienced surgeons. MAIN OUTCOME MEASURES: NZCRS system uptake and adherence, appropriate identification of high risk cases and intraoperative complication rates. RESULTS: NZCRS scores calculated in 500 of 621 (80.5%) cases and 98 (19.6%) scored as "high risk." Cataract surgery (N = 500) performed by: 12 Registrars (20%), 4 Fellows (7.2%), 26 Consultants (72.8%). Risk scores adhered to in 99%. Overall intraoperative complications (3.0%) included iris prolapse 1.6% and posterior capsule tear 0.8%. No statistical difference in complication rates identified between surgeon grades. Mean best-corrected visual acuity was 6/10 (20/32). Postoperatively, cystoid macular oedema occurred in 3.2%. Rescoring by an experienced investigator noted a greater number of "high risk scores" (31.6% vs 19.6%) related to differences in subjective scoring of anterior chamber depth and cataract density. CONCLUSIONS AND RELEVANCE: Practical uptake of cataract risk stratification was promising in this study with NZCRS calculated in 80.5% with 99% adherence to scoring recommendations. Compared to baseline studies, in the day-to-day clinical setting, a continued, decreasing trend in frequency and severity of intraoperative complications was noted. Subjective variability of risk scoring may be further improved by better, objective, standardization.

Comparison of corneal biomechanical properties following penetrating keratoplasty and deep anterior lamellar keratoplasty for keratoconus.

IMPORTANCE: Keratoplasty is a surgical procedure to create a more regular optical surface following biomechanical weakening of the cornea in keratoconus. The ideal keratoplasty procedure should also restore corneal biomechanics to that of the healthy cornea. BACKGROUND: This study aimed to evaluate and compare the biomechanical properties of corneas following penetrating keratoplasty (PKP) and predescematic deep anterior lamellar keratoplasty (DALK) to those of healthy eyes. DESIGN: Prospective cross-sectional study. PARTICIPANTS: Two cohorts of post-keratoplasty eyes (42 eyes with PKP and 27 eyes with DALK) with each other, and with a cohort of 152 healthy eyes. METHODS: All eyes were examined by slit-lamp biomicroscopy, tomography, anterior segment-OCT and non-contact tonometry CorVis ST (CST). MAIN OUTCOME MEASURES: CST biomechanical parameters, maximum corneal deformation (MCD) and corneal energy dissipation were compared between keratoplasty techniques, and with healthy eyes. RESULTS: The mean age of participants with PKP and DALK were 35 ± 13.7 and 36.1 ± 12.6 years, respectively. None of the CST parameters were significantly different between PKP and DALK eyes. However, when compared to healthy corneas, numerous parameters were significantly different for both keratoplasty techniques. Of note, MCD was significantly higher in PKP compared to DALK and healthy corneas, after controlling for co-factors. CONCLUSIONS AND RELEVANCE: Neither type of keratoplasty technique utilized in keratoconus completely restored corneal biomechanical properties to that of healthy corneas. However, PKP resulted in a greater number of parameters significantly different to healthy corneas, compared to DALK.

Microdroplet and spatter contamination during phacoemulsification cataract surgery in the era of COVID-19.

IMPORTANCE: Determine phacoemulsification cataract surgery risk in a Covid-19 era. BACKGROUND: SARS-CoV-2 (Covid-19) transmission via microdroplet and aerosol-generating procedures presents risk to medical professionals. As the most common elective surgical procedure performed globally; determining contamination risk from phacoemulsification cataract surgery may guide personal protection equipment use. DESIGN: Pilot study involving phacoemulsification cataract surgery on enucleated porcine eyes by experienced ophthalmologists in an ophthalmic operating theatre. PARTICIPANTS: Two ophthalmic surgical teams. METHODS: Standardized phacoemulsification of porcine eyes by two ophthalmologists accompanied by an assistant. Fluorescein incorporated into phacoemulsification irrigation fluid identifying microdroplets and spatter. Contamination documented using a single-lens reflex camera with a 532 nm narrow bandpass (fluorescein) filter, in-conjunction with a wide-field blue light and flat horizontal laser beam (wavelength 532 nm). Quantitative image analysis using Image-J software. MAIN OUTCOME MEASURES: Microdroplet and spatter contamination from cataract phacoemulsification. RESULTS: With phacoemulsification instruments fully within the eye, spatter contamination was limited to <10 cm. Insertion and removal of the phacoemulsification needle and bimanual irrigation/aspiration, with irrigation active generated spatter on the surgeons' gloves and gown extending to >16 cm below the neckline in surgeon 1 and > 5.5 cm below the neckline of surgeon 2. A small tear in the phacoemulsification irrigation sleeve, presented a worse-case scenario the greatest spatter. No contamination above the surgeons' neckline nor contamination of assistant occurred. CONCLUSIONS AND RELEVANCE: Cataract phacoemulsification generates microdroplets and spatter. Until further studies on SARS-CoV-2 transmission via microdroplets or aerosolisation of ocular fluid are reported, this pilot study only supports standard personal protective equipment.

In vivo confocal microscopy of the inflamed anterior segment: A review of clinical and research applications.

In vivo confocal microscopy (IVCM) allows non-invasive imaging of the living human cornea, specifically enabling the detection of immune cells in the healthy and diseased ocular anterior segment. Studies using IVCM have provided insight into the effects of contact lens wear on corneal Langerhans cell density and morphology, and the effects of eye drops on conjunctiva-associated lymphoid tissue. IVCM has also been shown to be a useful adjunctive diagnostic tool in distinguishing infective and non-infective uveitis and in diagnosing atypical infective keratitis. In the research setting, this technology has enhanced our understanding of the role of inflammatory cells in corneal neuropathy and angiogenesis. In vivo-ex vivo correlation using animal models has helped overcome some of the difficulties in identifying cell type on IVCM images. As highlighted in this review, currently there are multiple established, and emerging, clinical and research applications for IVCM in the inflamed anterior segment.

Cystoid macular oedema following cataract surgery: A review.

Pseudophakic cystoid macular oedema (PCMO) remains a significant cause of compromised postoperative vision in contemporary cataract surgery. Well-established risk factors include intraoperative complications such as posterior capsule rupture and preoperative factors including: diabetes mellitus, uveitis, retinal vein occlusion, epiretinal membrane. The role of topical glaucoma medications in PCMO continues to be debated. Current treatment strategies largely target suppression of inflammation. Topical NSAIDs remain the mainstay in prophylaxis and treatment of PCMO. Topical corticosteroids are commonly used as monotherapy or in combination with NSAIDs. Unfortunately, high-quality trials are notably lacking for other PCMO treatment modalities such as: periocular corticosteroids, orbital floor triamcinolone, intravitreal triamcinolone, corticosteroid implants, intravitreal bevacizumab and pars-plana vitrectomy. A lack of consistency in defining PCMO and resolution of PCMO explains why even large systematic reviews may come to contradictory conclusions. This review explores the varied contemporary evidence-base in relation to the aetiology, diagnosis, prophylaxis and treatment of PCMO.

Repeat corneal transplantation in Auckland, New Zealand: Indications, visual outcomes and risk factors for repeat keratoplasty failure.

IMPORTANCE: In New Zealand, repeat keratoplasty has become the second leading indication for corneal transplantation. BACKGROUND: To report the indications, outcomes and survival of repeat keratoplasty and evaluate the risk factors for graft failure. DESIGN: Retrospective study in a public corneal service. PARTICIPANTS: Two hundred nineteen patients undergoing 279 repeat keratoplasty procedures during 1991-2017. METHODS: The New Zealand National Eye Bank prospectively collects data on all corneal transplants. This was utilized to identify patients undergoing repeat keratoplasty in Auckland. Clinical records were retrospectively reviewed. MAIN OUTCOME MEASURES: Graft survival and visual outcome. RESULTS: The repeat keratoplasty technique was penetrating keratoplasty (PK) in 242 cases (86.7%) and endothelial keratoplasty in 37 (13.3%). The most common primary indication was keratoconus (46.6%). The most common indication for repeat keratoplasty was endothelial decompensation (37.6%). For PK performed as a repeat keratoplasty, the median survival in years was 12.0 for first, 3.5 for second and 2.3 for third repeat keratoplasty. Keratoconus had the longest graft survival (median 13.0 years). In surviving grafts, median visual acuity was 6/15 at 1 year and 6/12 at 2 years. On multivariate analysis, regraft number (P = .022), non-European ethnicity (P = .007), concurrent surgical procedure (P < .0005), lower donor endothelial density (P = .028), previous glaucoma surgery (P < .0005), postoperative raised intraocular pressure (P = .001) and graft rejection (P = .032) were associated with keratoplasty failure. CONCLUSIONS AND RELEVANCE: Repeat keratoplasty survival is affected by multiple interacting factors and prognosis worsens with each subsequent regraft. These results will help guide clinicians in addressing patients' individual risk factors when embarking on repeat corneal transplant surgery.

Advanced anterior segment imaging in keratoconus: a review.

Advances in anterior segment imaging have enhanced our ability to detect keratoconus in its early stages and characterize the pathologic changes that occur. Computerized corneal tomography has elucidated the alterations in shape of the anterior and posterior corneal surfaces and alterations in thickness as the disease progresses. Automated screening indices such as the keratoconus screening index were developed to assist in detecting keratoconus in suspicious cases. In vivo assessment of keratoconic corneas has revealed that compromised corneal biomechanics can now be measured clinically. Optical coherence tomography has demonstrated alterations in corneal epithelial thickness and distribution in keratoconus, has a role in assessing Descemet's membrane detachment in acute corneal hydrops (ACH) and the depth of the demarcation line following corneal collagen cross-linking. In vivo confocal microscopy has exhibited cellular changes that occur in keratoconus and provided insight into cellular events that may be related to the development of neovascularization in ACH.

The rising tide of Acanthamoeba keratitis in Auckland, New Zealand: a 7-year review of presentation, diagnosis and outcomes (2009-2016).

IMPORTANCE: Acanthamoeba is an increasingly prevalent cause of vision-threatening microbial keratitis. BACKGROUND: To assess the incidence, clinical presentation, diagnosis and outcomes of patients with Acanthamoeba keratitis (AK) in Auckland, New Zealand over a 7-year period. DESIGN: Retrospective observational consecutive case series. PARTICIPANTS: Fifty-eight eyes of 52 patients diagnosed with AK. METHODS: All cases of AK were identified using a cross-referenced search of clinical, laboratory and pharmacy records from March 2009 to May 2016. MAIN OUTCOME MEASURES: Demographic and clinical data were collected including age, gender, risk factors, clinical manifestations, initial diagnosis, diagnostic investigations, treatment, presenting and final visual acuity and surgical interventions. RESULTS: Contact lens (CL) use was noted in 96% of unilateral and 100% of bilateral cases. The mean duration of symptoms at presentation was 21 days and the mean duration from presentation to definitive diagnosis was 14 days. Initial diagnosis was recorded as CL-related keratitis in 70.6%, viral keratitis in 15.5% and AK in 12.0%. The diagnosis was confirmed with In vivo confocal microscopy (IVCM) in 67.2%, corneal scrape in 22.4%, corneal biopsy in 1.7% and clinically in 8.6%. IVCM sensitivity was 83.0%. Surgical intervention was required in four patients, all with delayed diagnosis (range 63-125 days). The incidence of AK has more than doubled when compared with the preceding 7-year period. CONCLUSIONS AND RELEVANCE: AK is a rare vision-threatening protozoal infection with rapidly-increasing incidence in New Zealand, predominantly affecting CL users. Diagnosis is often challenging and when delayed is associated with worse outcomes. IVCM offers rapid diagnosis with high sensitivity.

Systemic associations of corneal deposits: a review and photographic guide.

The cornea may be considered 'the window to the body', with numerous systemic diseases exhibiting corneal manifestations. Indeed, the cornea is often the presenting sign of such diseases. This article provides a concise review and photographic guide to a range of types of corneal deposition that may be observed secondary to systemic disease.

Auckland cataract study 2: clinical outcomes of phacoemulsification cataract surgery in a public teaching hospital.

IMPORTANCE: A contemporary benchmark for the most common ophthalmic surgery. BACKGROUND: To assess patient characteristics and outcomes of contemporary phacoemulsification cataract surgery in a New Zealand public teaching hospital setting. DESIGN: Prospective observational study. PARTICIPANTS: Consecutive cases (n = 500) of phacoemulsification surgery between April and June 2015. METHODS: An independent observer assessed clinical and surgical data preoperatively and 4-6 weeks postoperatively. MAIN OUTCOME MEASURES: Visual acuity, intraoperative and postoperative complications. RESULTS: Mean age was 72.3 ± 11.9 years and 57% female. Mean preoperative best-measured visual acuity was 6/30. Ocular comorbidity was present in 45.8% of eyes, most commonly glaucoma (10%), age-related macular degeneration (8%) and diabetic retinopathy (8%). Systemically, hypertension (59%) and diabetes mellitus (31%) were prevalent. Mean contralateral best-measured visual acuity was 6/12 (n = 495) with 62% being phakic. The rate of posterior capsular tear was 2.6% and cystoid macular oedema 3.5%. Intraoperative complication rates were not significantly different between surgeon levels (P = 0.234). However, registrars had fewer postoperative complications than fellows (2.2% vs. 11.9%, P = 0.012). Postoperatively, mean unaided and best-measured visual acuity were 6/12 and 6/9. CONCLUSIONS AND RELEVANCE: This study reports current phacoemulsification surgery outcomes in a major public teaching institution. A large proportion of patients exhibited systemic and ocular comorbidities, relatively dense cataracts and poor presenting visual acuity. However, visual outcomes and intraoperative complication rates were not statistically different between trainees and senior surgeons. Generally, outcomes reflect international standards and have improved since the last comparable study in this region.

Impact of diabetes mellitus on the ocular surface: a review.

Although diabetes mellitus is reaching epidemic proportions worldwide, ocular surface complications are still largely believed to be uncommon. Although these complications are not often sight threatening, the general well-being of patients and the cost of their health care can be respectively compromised and added by them. Over the last decade, an association of ocular surface complications (in particular reduced corneal sub-basal nerve density and corneal sensitivity) with peripheral neuropathy has emerged, which could help recognize the development of peripheral complications at an earlier stage and also provide research opportunities for examining new treatment modalities of diabetic neuropathies. The ocular surface complications of diabetes mellitus and their association with peripheral neuropathy are reviewed by this report.

Demographics and ocular biometric characteristics of patients undergoing cataract surgery in Auckland, New Zealand.

BACKGROUND: The aim is to investigate ethnic variation, in presentation and biometric parameters, within the population undergoing cataract surgery in Auckland. DESIGN: The design is a retrospective study. PARTICIPANTS: Four thousand nine hundred thirty-one eyes of 3524 consecutive patients undergoing cataract surgery in Auckland Public Hospital over 18 months were included in the study. METHODS: Analysis of preoperative medical records was performed. MAIN OUTCOME MEASURES: Age, gender, self-reported ethnicity, keratometry, anterior chamber depth, axial length and intraocular lens (IOL) power data were collected. RESULTS: Maori (4.7%) were under-represented compared with the proportion of Maori attending the eye clinic (5.5%) and in the major patient catchment area (8.2%). People of Maori, Pacific and Indian ethnicities presented at a significantly younger age (66.4, 65.9 and 67.9 years, respectively) than those of Caucasian and Asian ethnicities (76.4 and 71.3 years, respectively, P < 0.001). Advanced cataract was more likely in Pacific peoples and Maori than Caucasians. The mean axial length was longest in Asian eyes (23.83 ± 1.52 mm). The mean anterior chamber depth in the eyes of Pacific peoples (3.20 ± 0.39 mm) was significantly greater than that of Caucasians (3.09 ± 0.42 mm, P = 0.001) and Asians (3.05 ± 0.49 mm, P < 0.001). The mean IOL power in Asian eyes was 19.45D. This was significantly lower than the IOL power required by Caucasian (20.72D, P < 0.001) and Pacific ethnicities (20.61D, P = 0.001). With-the-rule astigmatism was highly prevalent in Maori and Pacific peoples, whereas in all other ethnicities, against-the-rule astigmatism was more common. CONCLUSIONS: This study identified significant ethnic variation in presentation for cataract surgery and ocular biometric parameters. These data may help identify potential biometric refinements and those at risk of developing ocular morbidities known to be associated with these parameters.

The pathophysiology of Fuchs' endothelial dystrophy--a review of molecular and cellular insights.

Fuchs' endothelial corneal dystrophy (FECD) is the most common corneal endothelial dystrophy and commonly results in loss of vision. This review highlights the advances in our understanding of the pathophysiology of FECD through in vivo confocal microscopy (IVCM) and in vitro studies. All layers of the cornea may be affected by FECD, either primarily or secondary to corneal oedema. The primary changes include reduction of endothelial cell density and changes to endothelial morphology. Thickening of Descemet's membrane occurs, with addition of collagenous layers and formation of guttae. Changes secondary to corneal oedema include formation of epithelial bullae and sub-epithelial fibroblast and collagen infiltration, reduction of sub-basal corneal nerve density, and reduced anterior keratocyte density and fibroblastic transformation of stressed keratocytes in the stroma. Many of the microstructural changes occurring in FECD may be observed with IVCM, and these observations correlate well with histological studies. IVCM studies of early and mid-stage FECD are likely to provide further insight into the sequence of pathological processes that occur in this disease.

The Effects of Re-challenge in Patients with a History of Acute Anterior Uveitis Following Intravenous Zoledronate.

To determine the incidence of adverse ocular side effects following re-challenge in patients who previously developed ocular symptoms following intravenous zoledronate. Secondary data analysis of a large, prospective, randomized, double-blind, placebo-controlled clinical trial was performed. Participants consisted of postmenopausal females with osteopenia randomized to placebo (N = 1000) or zoledronate 5 mg (N = 1001) intravenous infusion. Recruitment occurred over a 2-year period, with the first infusion being administered at recruitment, and subsequent infusions every 18 months. Eight participants developed acute anterior uveitis (AAU) (diagnosed by an ophthalmologist) following the first infusion of zoledronate. Following appropriate ophthalmic treatment, no patients had visual loss or other ocular sequelae. One further participant reported "sore red eyes" but did not attend for ophthalmology review. Six participants declined further infusions. The remaining three participants were administered two further zoledronate infusions, 18 months apart, and none developed any ocular symptoms following each infusion. As a precaution, two of these participants were examined by an ophthalmologist 3 days after their second infusion and neither had ocular symptoms or signs of AAU and no subsequent ocular side effects. AAU following zoledronate infusion is likely to be part of the acute phase response. If treated promptly under the care of an ophthalmologist, the visual prognosis is excellent. The results of this study suggest that the development of AAU should not be a contraindication to further infusion. However, in such cases, patients should be warned of the symptoms of AAU (ocular pain, redness, photophobia or blurred vision) and should be promptly referred to an ophthalmologist if symptoms develop.

In vivo confocal microscopy analyses of corneal microstructural changes in a prospective study of collagen cross-linking in keratoconus.

PURPOSE: To use in vivo confocal microscopy (IVCM) to quantitatively analyze microstructural changes over time, after corneal collagen cross-linking for keratoconus. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 38 eyes of 38 patients undergoing collagen cross-linking for keratoconus. METHODS: Prospective, clinical cohort study of corneal collagen cross-linking in progressive keratoconus. Laser scanning IVCM performed preoperatively and at 1, 3, 6, and 12 months postoperatively. MAIN OUTCOME MEASURES: Density of corneal sub-basal nerves, anterior and posterior keratocytes, and corneal endothelium. RESULTS: Compared with baseline values, the mean sub-basal nerve density decreased significantly at 1, 3, and 6 months postoperatively (P < 0.01); however, this returned to preoperative values at 12 months (P = 0.57). One month postoperatively, there was complete absence of keratocyte nuclei in 86% of corneas. Anterior stromal edema with hyper-reflective cytoplasm and extracellular lacunae in a honeycomb-like appearance was observed and persisted at 3 months postoperatively. Scattered, presumed fragmented keratocyte nuclei, were observed at 1 and 3 months, but by 6 months, keratocyte repopulation of the anterior stroma was apparent. Quantitative analysis confirmed a significant decrease in the mean anterior keratocyte density 1, 3, and 6 months postoperatively (P ≤ 0.01) with return to baseline values at 12 months postoperatively (P = 0.57). The demarcation between treated and untreated corneal stroma appeared as a region where normal keratocytes transitioned into elongated, hyper-reflective, needle-like structures and then into large hyper-reflective stromal bands. There was no significant change in posterior keratocyte density or endothelial density at any postoperative time point. CONCLUSIONS: This prospective IVCM study revealed complete loss of the sub-basal nerve plexus and loss of anterior stromal keratocytes in the early postoperative period, with complete regeneration of the sub-basal nerve plexus and keratocyte repopulation by 12 months postoperatively. The posterior stroma and corneal endothelium were unaffected.