Systemic risk factors of dry eye disease subtypes: A New Zealand cross-sectional study.

PURPOSE: To evaluate systemic risk factors of dry eye disease, aqueous tear deficiency, and meibomian gland dysfunction. METHODS: Three hundred and seventy-two community residents (222 females, 150 males; mean ± SD age, 39 ± 22 years) were recruited in a cross-sectional study. Past medical history, dry eye symptomology, ocular surface characteristics, and tear film quality were evaluated for each participant within a single clinical session. The diagnosis of dry eye disease, aqueous tear deficiency, and meibomian gland dysfunction were based on the global consensus recommendations of the Tear Film and Ocular Surface Society's Dry Eye Workshop II (TFOS DEWS II) and International Workshop on Meibomian Gland Dysfunction. RESULTS: Overall, 109 (29%) participants fulfilled the TFOS DEWS II criteria for dry eye disease, 42 (11%) had aqueous tear deficiency, and 95 (26%) had meibomian gland dysfunction. Multivariate logistic regression analysis demonstrated that systemic rheumatologic disease and antidepressant medication were independently associated with aqueous tear deficiency (both p < 0.05). Significant risk factors for meibomian gland dysfunction included age, East Asian ethnicity, migraine headaches, thyroid disease, and oral contraceptive therapy (all p ≤ 0.01). CONCLUSIONS: Both etiological subtypes of dry eye disease were associated with a number of systemic risk factors. These findings would support routine systemic inquiry of dry eye disease and associated systemic conditions and medications, in order to facilitate opportunistic screening and timely inter-disciplinary referral where necessary.

Randomised double-masked placebo-controlled trial of the cumulative treatment efficacy profile of intense pulsed light therapy for meibomian gland dysfunction.

PURPOSE: To assess long-term cumulative treatment effects of intense pulsed light (IPL) therapy in meibomian gland dysfunction (MGD). METHODS: Eighty-seven symptomatic participants (58 female, mean ± SD age, 53 ± 16 years) with clinical signs of MGD were enrolled in a prospective, double-masked, parallel-group, randomised, placebo-controlled trial. Participants were randomised to receive either four or five homogeneously sequenced light pulses or placebo treatment to both eyes, (E-Eye Intense Regulated Pulsed Light, E-Swin, France). Visual acuity, dry eye symptomology, tear film parameters, and ocular surface characteristics were assessed immediately before treatment on days 0, 15, 45, 75, and four weeks after treatment course completion on day 105. Inflammatory and goblet cell function marker expression, and eyelid swab microbiology cultures were evaluated at baseline and day 105. RESULTS: Significant decreases in OSDI, SPEED, and SANDE symptomology scores, and meibomian gland capping, accompanied by increased tear film lipid layer thickness, and inhibited Corynebacterium macginleyi growth were observed in both treatment groups (all p < 0.05). Sustained clinical improvements occurred in both treatment groups from day 75, although significant changes from day 45, in lipid layer quality, meibomian gland capping, OSDI and SANDE symptomology, were limited to the five-flash group (all p < 0.05). CONCLUSIONS: IPL therapy effected significant improvements in dry eye symptomology, tear film lipid layer thickness, and meibomian gland capping in MGD patients. Five-flash IPL treatment showed superior clinical efficacy to four-flash, and an initial course of at least four treatments is suggested to allow for establishment of sustained cumulative therapeutic benefits prior to evaluation of overall treatment efficacy. TRIAL REGISTRATION NUMBER: ACTRN12616000667415.

Corneal Transplantation in New Zealand 2000 to 2009.

PURPOSE: To quantify all minor/major adverse events in a large cohort of consecutive corneal transplants, particularly in respect to penetrating keratoplasty (PKP). METHODS: All corneal transplants in the Auckland region over a 10-year period (2000-2009) were identified through the New Zealand National Eye Bank. Relevant clinical records were assessed for this period and 2 years after. All intraoperative or postoperative adverse events/complications, visual acuity, and graft outcomes were recorded. RESULTS: Detailed data were available for 941 (94.5%) of 996 procedures in the study period, including 834 PKPs, 73 deep anterior lamellar keratoplasties, 28 Descemet stripping endothelial keratoplasties, and 6 tectonic keratoplasties. Intraoperative adverse events occurred in 117 (12.4%) procedures, most commonly positive vitreous pressure (6.3%). Postoperative adverse events included elevated intraocular pressure (21.3%, >30 mm Hg), graft rejection (29.8%), suture-related complications (30.1%), dry eye (15.9%), epithelial defect (9.8%), wound compromise (3.4%), microbial keratitis (3.2%), and endophthalmitis (0.6%). At 2 years, 58.7% of eyes achieved best-corrected visual acuity of ≥6/12 (20/40) and 69.6% achieved ≥6/18 (20/60). Graft survival at 2 years was 87.9%, 92.3%, and 100% for PKP, deep anterior lamellar keratoplasty, and Descemet stripping endothelial keratoplasty, respectively. CONCLUSIONS: In this study of 941 consecutive, principally penetrating, corneal transplants, adverse events were found to be more common than typically reported. In an era in which PKP is increasingly substituted by lamellar surgery, this provides useful insight into operative and postoperative adverse events in penetrating surgery.

Descemet's membrane macroperforation during interface irrigation in big bubble deep anterior lamellar keratoplasty.

This report describes the macroperforation of descemet's membrane (DM) during irrigation of the interface following successful removal of stromal tissue in big bubble (BB) deep anterior lamellar keratoplasty (DALK). A 42-year-old woman with keratoconus underwent a BB DALK procedure. After successful formation of Type 2 bubble and removal of stromal tissue, interface irrigation was performed to remove residual viscoelastic. This led to a macroperforation of DM, and the case was converted to penetrating keratoplasty. To the best of our knowledge, this is the first report of such a complication in the literature. Recognition of a 2 bubble formation during pneumodissection should alert the surgeon to a high risk of DM rupture. We advise against the removal of DM from the donor in such cases as an added measure of safety.

A comparison of the self-reported dry eye practices of New Zealand optometrists and ophthalmologists.

PURPOSE: The aim of this cross-sectional survey was to evaluate the self-reported clinical practices of New Zealand optometrists and ophthalmologists with respect to the diagnosis and management of dry eye disease. It also sought to compare these behaviours with the current research evidence base. METHODS: An anonymous survey was distributed electronically to New Zealand eye care clinicians (optometrists n = 614, ophthalmologists n = 113) to determine practitioner interest in dry eye disease, practice experience, practice modality, preferred diagnostic and management strategies, and information used to guide patient care. RESULTS: Respondents from both professions (response rates, optometrists: 26%, ophthalmologists: 26%) demonstrated similarly strong knowledge of tear film assessment. Ninety percent of respondents ranked patient symptoms and meibomian gland evaluation as the most valuable and common diagnostic approaches. Conversely, standardised grading scales and validated dry eye questionnaires were infrequently adopted. Both professions tailored dry eye management according to severity, indicating eyelid hygiene and non-preserved lubricants as mainstay therapies. Ophthalmologists prescribed systemic tetracyclines significantly more often than optometrists for moderate (48% vs 11%) and severe (72% vs 32%) dry eye (p < 0.05). Continuing education conferences were acknowledged as the primary information source used to guide dry eye management practices by both professions. CONCLUSIONS: Consistent with evidence-based guidelines, New Zealand eye care professionals combine subjective and objective techniques to diagnose and stratify dry eye management according to disease severity. There is potential to improve dissemination of research evidence into clinical practice, with continuing education via professional conferences the favoured mode of delivery.

Connexin hemichannel induced vascular leak suggests a new paradigm for cancer therapy.

It is 40 years since cancer growth was correlated with neovascularisation. Anti-angiogenic drugs remain at the forefront of cancer investigations but progress has been disappointing and unexpected toxicities are emerging. Gap junction channels are implicated in lesion spread following injury, with channel blockers shown to improve healing; in particular preventing vascular disruption and/or restoring vascular integrity. Here we briefly review connexin roles in vascular leak and endothelial cell death that occurs following acute wounds and during chronic disease, and how connexin channel regulation has been used to ameliorate vascular disruption. We then review chronic inflammatory disorders and trauma in the eye, concluding that vascular disruption under these conditions mimics that seen in tumours, and can be prevented with connexin hemichannel modulation. We apply this knowledge to tumour vessel biology, proposing that contrary to current opinion, these data suggest a need to protect, maintain and/or restore cancer vasculature. This may lead to reduced tumour hypoxia, promote the survival of normal cells, and enable improved therapeutic delivery or more effective radiation therapy.

Regulation of connexin43 gap junction protein triggers vascular recovery and healing in human ocular persistent epithelial defect wounds.

Transiently blocking the expression of the gap junction protein connexin43 using antisense oligodeoxynucleotides or blocking hemichannels with connexin mimetic peptides has been shown to significantly improve outcomes in a range of acute wound models. Less is known about their likely effects in nonhealing wounds. In the eye, prolonged inflammation and lack of epithelial recovery in nonhealing corneal epithelial wounds may lead to corneal opacity, blindness or enucleation. We report here the first human applications of antisense oligodeoxynucleotides that transiently block translation of connexin43 in a prospective study of five eyes with severe ocular surface burns (persistent epithelial defects), which were unresponsive to established therapy for 7 days to 8 weeks prior to treatment. Connexin43-specific antisense oligodeoxynucleotide was delivered in cold, thermoreversible Poloxamer407 gel under either an amniotic membrane graft or a bandage contact lens. The connexin43-specific antisense application reduced inflammation within 1-2 days, and in all five eyes complete and stable corneal reepithelialization was obtained. Recovery of the vascular bed and limbal reperfusion appeared to precede corneal epithelial recovery. We conclude that connexin modulation provides a number of benefits for nonhealing ocular burn wounds, one of which is to promote vascular recovery.

Publication and citation analysis of the Australian and New Zealand Journal of Ophthalmology and Clinical and Experimental Ophthalmology over a 10-year period: the evolution of an ophthalmology journal.

PURPOSE: To analyse the pattern of change in publication content and citations generated by a mid-ranking ophthalmology journal as it evolved from the Australian and New Zealand Journal of Ophthalmology (ANZJO) to its successor, Clinical 0mp; Experimental Ophthalmology (CEO). METHODS: The Science Citation Index was used to analyse the publications of ANZJO and CEO over two 10-year periods (1990-1999 and 2000-2009, respectively). Publication and citation patterns were analysed in terms of source authors, institutions and countries. As a secondary measure, journal impact factors (JIFs) were retrieved from the Journal Citation Reports at the end of each period. RESULTS: Over the specified periods, 859 articles published in ANZJO were cited 1210 times, and 1529 articles published in CEO were cited 5374 times. Australia was the largest contributing country to both journals; however, the proportional contributions from other countries including New Zealand, UK, USA, India and China increased significantly in CEO. Articles were cited by authors from 793 institutions in 60 countries for ANZJO and 2997 institutions in 95 countries for CEO. The contribution by key authors (identified as the top 10 most-published authors) towards total journal publications was 24% in ANZJO, but only 16% in CEO; however, these publications were responsible for 26.6% and 28.8% of the total citations, respectively. With respect to the most recent JIFs, ANZJO was 0.433 in 1999 (ranked 33 of 43 journals) and CEO was 1.35 in 2008 (ranked 27 of 48 journals). CONCLUSION: CEO has substantially increased the number of publications, citation counts and international sources compared with its well-established predecessor, ANZJO, over the assessed periods. CEO also appears to have a higher international profile with increasing citations counts from more countries. This evolution from a regional, to a more international, journal has been substantial and is reflected by a significant increment in JIF, and a modest increase in overall JIF-ranking, for CEO.

Acanthamoeba keratitis and contact lens wear.

Acanthamoeba keratitis is a rare but serious complication of contact lens wear that may cause severe visual loss. The clinical picture is usually characterised by severe pain, sometimes disproportionate to the signs, with an early superficial keratitis that is often misdiagnosed as herpes simplex virus (HSV) keratitis. Advanced stages of the infection are usually characterised by central corneal epithelial loss and marked stromal opacification with subsequent loss of vision. In this paper, six cases of contact lens-related Acanthamoeba keratitis that occurred in Australia and New Zealand over a three-year period are described. Three of the patients were disposable soft lens wearers, two were hybrid lens wearers and one was a rigid gas permeable lens wearer. For all six cases, the risk factors for Acanthamoeba keratitis were contact lens wear with inappropriate or ineffective lens maintenance and exposure of the contact lenses to tap or other sources of water. All six patients responded well to medical therapy that involved topical use of appropriate therapeutic agents, most commonly polyhexamethylene biguanide and propamidine isethionate, although two of the patients also subsequently underwent deep lamellar keratoplasty due to residual corneal surface irregularity and stromal scarring. Despite the significant advances that have been made in the medical therapy of Acanthamoeba keratitis over the past 10 years, prevention remains the best treatment and patients who wear contact lenses must be thoroughly educated about the proper use and care of the lenses. In particular, exposure of the contact lenses to tap water or other sources of water should be avoided.

Assessing the accuracy of Orbscan II post-LASIK: apparent keratectasia is paradoxically associated with anterior chamber depth reduction in successful procedures.

PURPOSE: To establish a relationship between the forward protrusion of the cornea (keratectasia), following successful LASIK, and anterior chamber depth. METHODS: One hundred and fifteen eyes of 59 patients who had undergone Zyoptix LASIK and 39 eyes of 21 patients who had undergone PlanoScan LASIK at the Eye Institute, Centre for Refractive Surgery, Remuera, Auckland, New Zealand, were included in the study. The results of Orbscan II acquisitions, taken before and 8.3 weeks +/- 4.0 (mean +/- standard deviation) following the procedure, were analysed to determine the amount of forward protrusion of the central 2 mm diameter of the posterior surface. The apparent keratectasia was then related to the Orbscan II anterior chamber depth (ACD) measurement in a linear mixed model analysis that included 'right or left eye', 'sex', 'type of LASIK procedure', 'change in pachymetry', 'postoperative pachymetry', 'change in anterior corneal curvature', 'postoperative anterior corneal curvature', 'planned ablation depth' and 'time until follow-up' as factors and covariates. RESULTS: The mean +/- SD amount of keratectasia determined by Orbscan II was 22.8 +/- 26.8 microm for the Zyoptix group and 16.9 +/- 24.6 microm for the PlanoScan group. The reduction in depth of the anterior chamber was 14.7 +/- 79.3 microm for the Zyoptix group and 18.2 +/- 68.8 microm for the PlanoScan group. The mixed model analysis demonstrated strong relationships with postoperative pachymetry and change in anterior corneal curvature (P < 0.001 and P < 0.001, respectively). Furthermore, the statistical model showed a marked significant difference in the Orbscan II assessment of keratectasia and change in ACD (P < 0.001). CONCLUSION: Using the Orbscan II device, the forward protrusion of the posterior corneal surface appears to coincide with a paradoxical reduction in depth of the anterior chamber. Although the keratectasia found in this study is accompanied by thin postoperative corneas and larger central pachymetry change, the contradictory decrease in anterior chamber depth creates uncertainty of measurement, and of ectasia as a mechanism of regression.

Higher-order aberrations of lenticular opacities.

PURPOSE: To measure and quantify higher-order aberrations induced by different types of lenticular opacities. SETTING: Department of Ophthalmology, University of Auckland, and Department of Ophthalmology, Auckland Public Hospital, Auckland, New Zealand. METHODS: Patients with lenticular opacities were recruited from outpatient clinics of a major tertiary referral center for ophthalmology. Patients were included if they had clinically evident, mild to moderate lenticular opacity with no coexisting ocular pathology. Patients were examined using standard preoperative techniques with additional assessment by wavefront aberrometry (Zywave, Bausch & Lomb) and Scheimpflug photography (EAS-1000, Nidek). For comparison, 20 eyes of 10 subjects with no lenticular opacity (control group) were recruited and assessed in an identical manner. RESULTS: Thirty persons were recruited and 40 eyes assessed, 20 with lenticular opacities. Ten eyes had predominantly cortical opacification, and 10 had mainly nuclear opacification. In eyes with predominantly cortical opacification, the mean logMAR uncorrected visual acuity (UCVA) was 0.5 +/- 0.2 (SD) (6/18 Snellen equivalent) and the mean logMAR best spectacle-corrected visual acuity (BSCVA), 0.2 +/- 0.2 (6/9). Analysis of aberrometry data for a 6.0 mm pupil in this group revealed an increase in coma of cosine phase (Z(3), P =.06) and tetrafoil of cosine phase (Z(4), P =.07) compared to eyes in the control group. Eyes with predominantly nuclear opacification had a mean logMAR UCVA of 0.7 +/- 0.2 (6/30) and a logMAR BSCVA of 0.4 +/- 0.2 (6/15). Aberrometry data for this cohort for a 6.0 mm pupil showed a statistically greater amount of spherical aberration (Z(4)(0), P =.001) and tetrafoil of cosine phase (Z(4), P =.005; Z(4)(-4), P =.004). CONCLUSIONS: This pilot study suggests that different types of early lenticular opacities induce different wavefront aberration profiles. Predominantly cortical opacification produced an increase in coma and nuclear opacification induced an increase in spherical aberration compared to eyes without opacities. Both types of lenticular opacities also induced a higher amount of tetrafoil. This could explain the significant visual symptoms in patients with early cataract and relatively good high-contrast Snellen acuity.

In vivo confocal microstructural analysis and surgical management of Brown-Mclean syndrome associated with spontaneous crystalline lens luxation.

We report 3 members of an extended family who presented with bilateral peripheral corneal edema consistent with Brown-McLean syndrome. On clinical examination, all eyes demonstrated normal central corneas and marked peripheral edema. In vivo confocal microscopy of the peripheral cornea highlighted similar observations in the 6 eyes including endothelial pigmentation, masked stromal structure due to edema, prominent nerves, and localized basal epithelial edema. In the central cornea, in vivo confocal microscopic observations highlighted large cellular structures with prominent nuclei in groups consisting of several cells of similar appearance. In vivo confocal microscopy may enhance the diagnosis of Brown-McLean syndrome and may be used for dynamic evaluation and postoperative follow-up of the structural corneal changes.