An optimized 3T MRI scan protocol to assess iris melanoma with subsequent histopathological verification - A prospective study.

INTRODUCTION: Magnetic resonance imaging (MRI) has demonstrated high levels of tissue contrast, accuracy and reproducibility in evaluating posterior uveal melanoma. Owing to smaller size, the role of MRI in detecting and characterising iris melanoma has not yet been explored. AIMS: To develop a protocol to image iris melanoma and describe the MRI characteristics of histopathological-confirmed iris melanoma. MATERIALS AND METHODS: An optimised MRI protocol, using a 3T MRI scanner and a 32-channel head coil, was developed to image iris tumours. A prospective, single-centre, 12-month study was conducted on all patients with lesions suspicious for iris melanoma. All patients were offered an MRI scan in addition to the standardised clinical procedures. Image quality comparison was made with existing clinical investigations. Iris melanoma characteristics on MRI are described. RESULTS: A successful optimised MRI scan protocol was developed that was able to detect and characterise iris melanoma. One normal participant and five patients with subsequent histopathological-confirmed iris melanoma (n = 6) were recruited. Four patients completed the full MRI sequence. All iris melanoma were detected on at least one T1- or T2-weighted images. When compared to the vitreous, all iris melanomas demonstrated hyper-intensity on T1-weighted images and hypo-intensity on T2-weighted images. On T1-mapping, T1-values of iris melanoma demonstrated an inverse relationship with the degree of tumour pigmentation. CONCLUSIONS: This study highlights an optimised, easily reproducible MRI scan protocol to image iris melanoma. Numerous MR imaging characteristics of iris melanoma are reported for the first time and a potential non-invasive tumour biomarker is described.

Behaviour of hTERT in the tears of neophyte contact lens wearers during the sleep/wake cycle.

PURPOSE: To investigate the behaviour of telomerase reverse transcriptase (hTERT) in the tears of healthy neophyte contact lenses-wearing individuals during the sleep/wake cycle. A subsequent aim was to investigate whether hTERT behaviour was associated with inflammatory mediators interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) in tears. METHODS: Flush tears were collected from 19 healthy, non-contact lens-wearing participants (11 males, 8 females, mean age 31.9 ± 5.7 years), before and during contact lens wear. Tears were collected at noon, before sleep and upon awakening and levels of hTERT, IL-6 and TNF-α, were determined using enzyme-linked immunosorbent assays (ELISA). RESULTS: hTERT levels (median [interquartile range]) during contact lens wear were significantly higher before sleep (436.5 (263.9 - 697.7) ng/ml compared to the same time point without contact lenses (256.1 (0.0 - 590.9) ng/ml (p = 0.01). There was no difference between contact lens wear (851.3 [353.2 - 2109.9]) ng/ml, and no wear (1091.0 [492.3 - 3045.4]) ng/ml, upon awakening (p = 0.94). A significant increase was found upon awakening compared to before sleep, irrespective of the presence of a contact lens (p = 0.02). IL-6 and TNF-α levels in tears were below the limit of detection. CONCLUSIONS: The study showed that hTERT increases after a contact lens is placed on the eye, but this change is small, compared to the impact of overnight eye closure. Taken together with the lack of responses of the inflammatory markers monitored at the same time points, this may suggest that hTERT can respond both to low-level stress stimuli acting on the ocular surface, and to situations where inflammation is a likely factor.

NLRP3 Inflammasome as a Potential Therapeutic Target in Dry Eye Disease.

Dry eye disease (DED) is a multifactorial ocular surface disorder arising from numerous interrelated underlying pathologies that trigger a self-perpetuating cycle of instability, hyperosmolarity, and ocular surface damage. Associated ocular discomfort and visual disturbance contribute negatively to quality of life. Ocular surface inflammation has been increasingly recognised as playing a key role in the pathophysiology of chronic DED. Current readily available anti-inflammatory agents successfully relieve symptoms, but often without addressing the underlying pathophysiological mechanism. The NOD-like receptor protein-3 (NLRP3) inflammasome pathway has recently been implicated as a key driver of ocular surface inflammation, as reported in pre-clinical and clinical studies of DED. This review discusses the intimate relationship between DED and inflammation, highlights the involvement of the inflammasome in the development of DED, describes existing anti-inflammatory therapies and their limitations, and evaluates the potential of the inflammasome in the context of the existing anti-inflammatory therapeutic landscape as a therapeutic target for effective treatment of the disease.

The Burden of Histologically Confirmed Uveal Melanoma in Aotearoa-New Zealand: A 21-year Review of the National Cancer Registry.

PURPOSE: The burden of uveal melanoma (UM) in Aotearoa-New Zealand (NZ), a country with the highest global burden of cutaneous melanoma, is unknown. This first, large-scale study of UM in NZ investigates survival and risks of mortality in histologically confirmed UM. METHODS: Deidentified epidemiological data on histologically confirmed UM between January 1, 2000, and December 31, 2020, were extracted from the NZ Cancer Registry. The main outcome measures were patient demographics, tumor characteristics, all-cause versus disease-specific survival, and risks of mortality. RESULTS: Histologically confirmed UM constituted 1.5% (n=703) of all-body site melanomas in NZ (n=47,997). UM predominantly affected Europeans (95%), followed by NZ indigenous Maori (4%), Asians (<1%), and Pacific Peoples (<1%), with no eye or sex predilection. Three hundred eighteen (45%) were deceased at follow-up. Of the deceased, 50% died from UM. The 1-, 5-, and 10-year survival from all-cause mortality was 94%, 68%, and 51%, and disease-specific survival was 97%, 79%, and 71%, respectively. Increasing age at UM diagnosis (>60 y), UM arising from nonspecified sites, and mixed cell UM were associated with an increased risk of disease-specific mortality. No difference in disease-specific mortality was found between sex and ethnicity on multivariate and competing risks analysis. CONCLUSIONS: Despite the government-funded public eye care and increasing research and awareness on UM globally, the burden of UM in the 21st century in NZ remains comparable to global studies. We continue to observe an earlier presentation of UM in non-European cohorts, particularly in our Maori population, and further studies on UM in NZ are warranted.

Conjunctival Melanoma in Aotearoa-New Zealand: A 21-Year Analysis of Incidence and Survival.

PURPOSE: Conjunctival melanoma (CM) is a rare and aggressive malignancy. Global studies demonstrate increased burden of disease in countries with high rates of cutaneous melanoma. There are currently no reports on CM incidence, trends, or survival within Aotearoa-New Zealand (NZ), a country with the highest global rates of cutaneous melanoma, which this study aims to address. DESIGN: This was a retrospective review using the national cancer registry. METHODS: Data on histologically confirmed CM diagnosed between January 1, 2000, and December 31, 2020, were obtained from the NZ Cancer Registry. Cases were identified using the International Classification of Disease, 10th edition (ICD-10) codes. Primary outcome measures were age-standardized incidence, trends, and survival. RESULTS: A total of 68 CM cases were identified. There was a preponderance for females (n=40, 58.8%) and CM predominantly affected European patients (n=63, 92.6%). Median follow-up was 5.0 years [interquartile range (IQR)=2.4-9.9 y] and the median age at diagnosis was 68.5 years (IQR=57.0-79.0 y), with non-Europeans presenting at a significantly younger age [-17.3 y (95% CI: -31.3 to -3.2), P =0.019] than Europeans. The annual age-adjusted incidence(±SD) was 0.6±0.2 cases per million population per year with a stable incidence trend over 21 years. All-cause mortality was found in 28 cases (41.2%) and the median time to death was 3.76 years (IQR=2.1-5.7 y). Five-year all-cause survival and disease-specific survival was 69% and 90%, respectively. CONCLUSIONS: This is the first report on CM incidence, trends, and mortality in NZ. The CM burden is in line with European and North American data, despite NZ having the highest rate of cutaneous melanoma. The incidence remained stable over 2 decades.

TFOS Lifestyle: Impact of nutrition on the ocular surface.

Nutrients, required by human bodies to perform life-sustaining functions, are obtained from the diet. They are broadly classified into macronutrients (carbohydrates, lipids, and proteins), micronutrients (vitamins and minerals) and water. All nutrients serve as a source of energy, provide structural support to the body and/or regulate the chemical processes of the body. Food and drinks also consist of non-nutrients that may be beneficial (e.g., antioxidants) or harmful (e.g., dyes or preservatives added to processed foods) to the body and the ocular surface. There is also a complex interplay between systemic disorders and an individual's nutritional status. Changes in the gut microbiome may lead to alterations at the ocular surface. Poor nutrition may exacerbate select systemic conditions. Similarly, certain systemic conditions may affect the uptake, processing and distribution of nutrients by the body. These disorders may lead to deficiencies in micro- and macro-nutrients that are important in maintaining ocular surface health. Medications used to treat these conditions may also cause ocular surface changes. The prevalence of nutrition-related chronic diseases is climbing worldwide. This report sought to review the evidence supporting the impact of nutrition on the ocular surface, either directly or as a consequence of the chronic diseases that result. To address a key question, a systematic review investigated the effects of intentional food restriction on ocular surface health; of the 25 included studies, most investigated Ramadan fasting (56%), followed by bariatric surgery (16%), anorexia nervosa (16%), but none were judged to be of high quality, with no randomized-controlled trials.

Long-term visual outcomes of children screened for retinopathy of prematurity with telemedicine in New Zealand.

CLINICAL RELEVANCE: Children with a history of regressed retinopathy of prematurity (ROP) are at increased risk of peripheral avascular retina. Wide-field digital retinal imaging and telemedicine is an effective tool for ROP screening. Ophthalmologists and Optometrists should have a high level of clinical suspicion for peripheral retinal changes in children screened for ROP. BACKGROUND: Retinopathy of prematurity, a vaso-proliferative disorder of the pre-term retina, is a preventable cause of childhood visual impairment. The Auckland Regional Telemedicine ROP (ART-ROP) network, established in 2006, utilises wide-field digital imaging and telemedicine to screen at-risk infants for ROP. This prospective observational study reports the long-term ocular outcomes of ART-ROP network infants. METHODS: A comprehensive paediatric eye examination including cycloplegic autorefraction and wide-field retinal imaging was completed on all participants. Participants had been screened for ROP by the ART-ROP network between May 2008 and October 2011. RESULTS: A total of 69 children, with a mean age of 5 to 8 years old were assessed and divided into two groups: those with or without a history of ROP, 44 and 25 children, respectively. Infants with a history of ROP had significantly lower gestational age (26.6 ± 1.9 vs. 29.1 ± 1.6 weeks, p < 0.001) and birth weight (937 ± 237 vs. 1177 ± 311 grams, p = 0.001). No significant differences were detected between the two groups for visual acuity (p = 0.596), stereopsis (p = 0.219), refractive error (p = 0.472), or strabismus. Clinically significant refractive error was noted in 10 participants; none with moderate or high myopia. Retinal imaging exposed asymptomatic, persistent, peripheral avascular retina in four children, all of whom had a history of regressed ROP. CONCLUSION: Visual and ocular outcomes did not vary based on history of ROP, with no participant having reduced vision as a result of undetected or untreated ROP. Further research is required into the long-term implication of persistent avascular retina in regressed ROP.

Corneal Nerve Changes Observed by In Vivo Confocal Microscopy in Patients Receiving Oxaliplatin for Colorectal Cancer: The COCO Study.

An objective method of early identification of people at risk of chemotherapy-induced peripheral neuropathy is needed to minimize long-term toxicity and maximize dose intensity. The aims of the study were to observe corneal nerve microstructure and corneal sensitivity changes and peripheral neuropathy in patients receiving oxaliplatin, and to determine its association with corneal parameters at different stages of treatment and assess utility as non-invasive markers to detect and monitor peripheral neuropathy. Twenty-three patients scheduled to receive oxaliplatin chemotherapy with intravenous 5-FU for gastro-intestinal cancer were recruited and followed up with for 12 months. Ocular examinations including corneal and retinal evaluations, alongside peripheral neuropathy assessment, were performed. The corneal nerve density did not show significant change after chemotherapy when measured with a widely used semi-automated program or an automated analysis technique. Macula and optic nerve function did not change during or after oxaliplatin chemotherapy. However, the corneal nerve density modestly correlated with clinical peripheral neuropathy after 20 weeks of chemotherapy (r = 0.61, p = 0.01) when peripheral neuropathy is typical most profound, and corneal nerve sensitivity correlated with neuropathy at 12 (r = 0.55, p = 0.01) and 20 weeks (r = 0.64, p = 0.006). In conclusion, corneal changes detected on confocal microscopy show moderate association with peripheral neuropathy, indicating their potential to identify the development of oxaliplatin-induced peripheral neuropathy. However, further studies are required to confirm these findings.

Corneal Confocal Microscopy in Type 1 Diabetes Mellitus: A Six-Year Longitudinal Study.

Purpose: The current study describes corneal nerve morphology using in vivo confocal microscopy (IVCM) in patients with type 1 diabetes (T1D) who were followed up for 6 years, and it examines the relationship between corneal parameters and metabolic control of glucose and peripheral neuropathy. Methods: Sixty-two participants (37 with T1D and 25 control participants) were assessed in 2011 and 2017. Participants with bilateral cataract surgery or controls who developed diabetes were excluded. All underwent HbA1c, IVCM, and central corneal sensitivity measurements at both time points in the eye previously examined. A modified total neuropathy score was obtained. Results: Participants were age and sex matched. The mean duration of diabetes was 32.1 ± 12.0 years at the follow-up visit. The sub-basal nerve density in participants with T1D was lower than that of the controls and did not change (mean ± SD, 11.07 ± 4.0 to 11.41 ± 4.1 mm/mm2; P = 0.71), but it showed a marginal change in controls (19.5 ± 3.7 to 21.63 ± 4.03 mm/mm2; P = 0.06). The corneal sensitivity in T1D did not change (1.3 ± 1.5 to 1.4 ± 1.0 mbar; P = 0.8), and it declined in the controls (0.2 ± 0.3 to 0.6 ± 0.3 mbar; P < 0.001). There were no significant changes in HbA1c (60.5 ± 12.5 to 61.6 ± 13.7 mmol/mol) or in modified total neuropathy scores (2.4 ± 3.2 to 3.4 ± 3.8; P = 0.2). Conclusions: The corneal nerve damage and poorer corneal sensitivity reported in the patients with T1D did not change and displayed improvement with good glycemic control. Translational Relevance: The corneal nerve changes may be of more value in those with a shorter duration of diabetes for the timely prediction of at-risk individuals likely to develop peripheral neuropathy, particularly in type 1 diabetes.

Case Series: Different Presentations of Iris Melanoma-Potential Masquerade of Benign and Malignant.

SIGNIFICANCE: Iris melanoma and iris nevi can be challenging to distinguish clinically. This case series provides unique insight into the rare condition and variable clinical presentations of iris melanoma. PURPOSE: This study aimed to highlight the varying clinical presentations of iris melanoma and to demonstrate the overlapping features of melanoma and nevi. CASE REPORTS: This case series includes five patients of varying age and sex who presented to clinic with pigmented iris lesions. These five patients have differing timeline to presentation and very different clinical presentations of their lesions. Clinical evaluation was based around the established "ABDCEF" guide for the assessment of malignant risk in iris lesions. The presentation of each lesion is discussed in relation to this guide and the experienced clinician's clinical suspicion of malignancy. When comparing the clinical suspicion with histological analysis, after biopsy, the result may be unexpected. Notably, initially benign nevi may transform into melanoma over time. These five cases were managed on an individual basis because the management and prognosis of iris melanomas vary significantly. Importantly, iris melanotic lesions have variable metastatic risk based on cytology and genetic predisposition. Informed consent was obtained from all the patients, institutional approval was obtained, and no identifiable health information is included in this case series. CONCLUSIONS: When presented with a pigmented iris lesion, clinicians must be vigilant with regular monitoring and have a low threshold for biopsy in pigmented lesions of high clinical suspicion.

The Aotearoa Research Into Keratoconus Study: Geographic Distribution, Demographics, and Clinical Characteristics of Keratoconus in New Zealand.

PURPOSE: To investigate the epidemiologic, demographic, and basic clinical characteristics of individuals with keratoconus managed by optometrists in New Zealand (NZ)/Aotearoa. METHODS: A prospective, longitudinal, nationwide, survey protocol was completed for every patient with keratoconus who underwent a consultation with participating optometrists in a 2-year period. Data for each patient included date of birth, sex, self-reported ethnicity, new or previous diagnosis, uncorrected (UCVA) and best-corrected visual acuity (BCVA), type of refractive correction required to obtain BCVA and keratometric readings obtained using keratometry or computerized topography. RESULTS: One thousand eight hundred sixty-nine cases were identified, with a mean age of 41.0 ± 15.7 years, 56.4% being men, and 87.3% with previous diagnosis. The distribution of cases was skewed toward Auckland (41.6%), Waikato (21.3%), Wellington (16.8%), and Bay of Plenty (13.3%). Self-reported ethnicities were predominantly NZ European (54.4%), Maori (24.7%), and Pacific Peoples (15.5%), disproportionate to the general population profile (74.0%, 14.9%, and 7.4% respectively). Most eyes (64.3%) were managed with rigid contact lenses (corneal lens in 34.2%). The mean K-mean was 49.0 ± 5.7 D. The mean UCVA was 6/42 and BCVA was 6/9. Maori and Pacific Peoples had both the highest K-mean and proportions of eyes graded stage IV on the Amsler-Krumeich scale. CONCLUSIONS: The results indicate that keratoconus is relatively common in NZ with at least 1869 patients managed by optometrists in 2 years. Most eyes had mild to moderate disease; however, Maori and Pacific Peoples seem to have greater disease severity. An ethnic predilection is apparent, with Maori and Pacific Peoples overrepresented relative to their population proportions, reinforcing a long-held clinical suspicion.

Corneal confocal microscopy demonstrates axonal loss in different courses of multiple sclerosis.

Axonal loss is the main determinant of disease progression in multiple sclerosis (MS). This study aimed to assess the utility of corneal confocal microscopy (CCM) in detecting corneal axonal loss in different courses of MS. The results were confirmed by two independent segmentation methods. 72 subjects (144 eyes) [(clinically isolated syndrome (n = 9); relapsing-remitting MS (n = 20); secondary-progressive MS (n = 22); and age-matched, healthy controls (n = 21)] underwent CCM and assessment of their disability status. Two independent algorithms (ACCMetrics; and Voxeleron deepNerve) were used to quantify corneal nerve fiber density (CNFD) (ACCMetrics only), corneal nerve fiber length (CNFL) and corneal nerve fractal dimension (CNFrD). Data are expressed as mean ± standard deviation with 95% confidence interval (CI). Compared to controls, patients with MS had significantly lower CNFD (34.76 ± 5.57 vs. 19.85 ± 6.75 fibers/mm2, 95% CI - 18.24 to - 11.59, P < .0001), CNFL [for ACCMetrics: 19.75 ± 2.39 vs. 12.40 ± 3.30 mm/mm2, 95% CI - 8.94 to - 5.77, P < .0001; for deepNerve: 21.98 ± 2.76 vs. 14.40 ± 4.17 mm/mm2, 95% CI - 9.55 to - 5.6, P < .0001] and CNFrD [for ACCMetrics: 1.52 ± 0.02 vs. 1.45 ± 0.04, 95% CI - 0.09 to - 0.05, P < .0001; for deepNerve: 1.29 ± 0.03 vs. 1.19 ± 0.07, 95% - 0.13 to - 0.07, P < .0001]. Corneal nerve parameters were comparably reduced in different courses of MS. There was excellent reproducibility between the algorithms. Significant corneal axonal loss is detected in different courses of MS including patients with clinically isolated syndrome.

Progressive corneal ectatic disease in pregnancy.

Pregnancy influences ocular changes which may exacerbate existing or develop new pathology. This review summarises the existing evidence on the association between pregnancy and progressive keratoconus or iatrogenic keratectasia. Ten online databases were searched systematically. Eligible studies were published in English and reported objective ophthalmic outcomes for women with evidence of (i) a new diagnosis of keratoconus, (ii) keratoconus progression or (iii) iatrogenic keratectasia following refractive surgery; during or within one year of pregnancy. Strength of evidence was assessed using the Oxford Centre for Evidence-Based Medicine levels of evidence. Seventeen articles have reported 33 peripartum women with new-onset or progressive ectasia, evident by signs of corneal hydrops or protrusion (n = 8); steepening on topography imaging (n = 20); a mean decline in best corrected visual acuity by +0.20 logMAR (95% CI -0.01 to +0.40, n = 23); a mean increase in maximum keratometry by 2.18 D (95% CI 1.44 to 2.91, n = 42); a mean decline in spherical equivalent refraction by -1.33 D (95% CI -1.73 to -0.93, n = 41); and a mean increase in astigmatism by -1.61 D (95% CI -2.46 to -0.75, n = 19). Pregnancy is associated with progressive ectasia in some women including those with previously stable keratoconus, or a history of laser-assisted in situ keratomileusis surgery or no history of corneal ectasia. This review highlights the heterogeneity in limited existing evidence, the need for a standardised definition of ectasia progression and further prospective studies for clinical guidelines. Closely monitoring women at risk may assist in early intervention with collagen cross-linking and prevent peripartum vision loss.

Combining In Vivo Corneal Confocal Microscopy With Deep Learning-Based Analysis Reveals Sensory Nerve Fiber Loss in Acute Simian Immunodeficiency Virus Infection.

PURPOSE: To characterize corneal subbasal nerve plexus features of normal and simian immunodeficiency virus (SIV)-infected macaques by combining in vivo corneal confocal microscopy (IVCM) with automated assessments using deep learning-based methods customized for macaques. METHODS: IVCM images were collected from both male and female age-matched rhesus and pigtailed macaques housed at the Johns Hopkins University breeding colony using the Heidelberg HRTIII with Rostock Corneal Module. We also obtained repeat IVCM images of 12 SIV-infected animals including preinfection and 10-day post-SIV infection time points. All IVCM images were analyzed using a deep convolutional neural network architecture developed specifically for macaque studies. RESULTS: Deep learning-based segmentation of subbasal nerves in IVCM images from macaques demonstrated that corneal nerve fiber length and fractal dimension measurements did not differ between species, but pigtailed macaques had significantly higher baseline corneal nerve fiber tortuosity than rhesus macaques (P = 0.005). Neither sex nor age of macaques was associated with differences in any of the assessed corneal subbasal nerve parameters. In the SIV/macaque model of human immunodeficiency virus, acute SIV infection induced significant decreases in both corneal nerve fiber length and fractal dimension (P = 0.01 and P = 0.008, respectively). CONCLUSIONS: The combination of IVCM and robust objective deep learning analysis is a powerful tool to track sensory nerve damage, enabling early detection of neuropathy. Adapting deep learning analyses to clinical corneal nerve assessments will improve monitoring of small sensory nerve fiber damage in numerous clinical settings including human immunodeficiency virus.

Deep learning-based analysis of macaque corneal sub-basal nerve fibers in confocal microscopy images.

BACKGROUND: To develop and validate a deep learning-based approach to the fully-automated analysis of macaque corneal sub-basal nerves using in vivo confocal microscopy (IVCM). METHODS: IVCM was used to collect 108 images from 35 macaques. 58 of the images from 22 macaques were used to evaluate different deep convolutional neural network (CNN) architectures for the automatic analysis of sub-basal nerves relative to manual tracings. The remaining images were used to independently assess correlations and inter-observer performance relative to three readers. RESULTS: Correlation scores using the coefficient of determination between readers and the best CNN averaged 0.80. For inter-observer comparison, inter-correlation coefficients (ICCs) between the three expert readers and the automated approach were 0.75, 0.85 and 0.92. The ICC between all four observers was 0.84, the same as the average between the CNN and individual readers. CONCLUSIONS: Deep learning-based segmentation of sub-basal nerves in IVCM images shows high to very high correlation to manual segmentations in macaque data and is indistinguishable across readers. As quantitative measurements of corneal sub-basal nerves are important biomarkers for disease screening and management, the reported work offers utility to a variety of research and clinical studies using IVCM.

Validation of Mahajan's formula for scaling ocular higher-order aberrations by pupil size.

Purpose: Zernike polynomials for describing ocular higher order aberrations are affected by pupil aperture. The current study aimed to validate Mahajan's formula for scaling Zernike polynomials by pupil size. Methods: Higher order aberrations for 3 intraocular lens models (AcrySof IQ IOL SN60WF, Technis ZA9003, Adapt Advanced Optics) were measured using the Zywave aberrometer and a purpose-built physical model eye. Zernike coefficients were mathematically scaled from a 5 mm to a 3 mm pupil diameter (5:3 mm), from a 5 mm to a 2 mm pupil diameter (5:2 mm), and from a 3 mm to a 2 mm pupil diameter (3:2 mm). Agreement between the scaled coefficients and the measured coefficients at the same pupil aperture was assessed using the Bland-Altman method in R statistical software. Results: No statistically significant mean difference (MD) occurred between the scaled and measured Zernike coefficients for 21 of 23 analyses after Holm-Bonferroni correction (P > 0.05). Mean differences between the scaled and measured Zernike coefficients were clinically insignificant for all aberrations up to the fourth order, and within 0.10 µm. Oblique secondary astigmatism (Z-24) was significantly different in the 5:3 mm comparison (MD = -0.04 µm, P < 0.01). Horizontal coma (Z13) was significantly different in the 3:2 mm comparison (MD = -0.07 µm, P = 0.03). There were borderline statistical differences in both vertical (Z-13) and horizontal coma (Z13) in the 5:3 mm comparison (MD = 0.02 µm, -0.09 µm, P = 0.05, 0.05, respectively). Conclusion: A formula for the scaling of higher order aberrations by pupil size is validated as accurate. Pupil scaling enables accurate comparison of individual higher order aberrations in clinical research for situations involving different pupil sizes.

Precision, agreement and utility of a contemporary non-contact corneal aesthesiometer.

BACKGROUND: The measurement of corneal sensitivity threshold is important for several ocular surface diseases. The current study assesses the precision, agreement and utility of corneal sensitivity threshold measurement using a new, purpose-built non-contact corneal aesthesiometer. METHODS: A new instrument and an established non-contact corneal aesthesiometer device was used to measure the corneal sensitivity threshold on the right eye of 40 healthy human participants. Exclusion criteria included: corneal pathology, previous ocular surgery, ocular trauma, contact lens wear, diabetes or peripheral neuropathy. A forced-response, double-staircase method was used to obtain corneal sensitivity threshold from the mean of three readings per participant, for each non-contact corneal aesthesiometer. Screen demarcations relative to the corneal limbus facilitated alignment with the new device. Repeatability of the new instrument was tested three consecutive times on the same day. Intra-observer and inter-observer reproducibility and agreement were determined using one-way analysis of variance or analysis of variance and Bland-Altman analysis, respectively. RESULTS: Forty eyes of 40 participants were assessed (15:25 M:F, 30.5 ± 11.4 years). The new instrument demonstrated good repeatability (p = 0.47). There was no difference in the mean corneal sensitivity threshold between the new (0.60 ± 0.36 mbar) and established (0.60 ± 0.34 mbar) aesthesiometers (p = 0.92). Utilising the new instrument, inter-observer reproducibility (on a different subset of 10 participants) yielded thresholds of 0.41 ± 0.16 mbar and 0.42 ± 0.13 mbar (p = 0.88) for the two observers. Bland-Altman analysis confirmed good intra and inter-observer agreement. Screen demarcations relative to the limbus, enabled easier corneal alignment. CONCLUSION: The new non-contact corneal aesthesiometer confirmed very good repeatability and reproducibility, as well as good agreement with the long-established instrument. Overall, this contemporary approach enables accurate and precise assessment of corneal sensitivity and thus, corneal nerve function, in normal and diseased cornea.

Auckland regional telemedicine retinopathy of prematurity screening network: A 10-year review.

IMPORTANCE: Retinopathy of prematurity (ROP) is a potentially blinding condition affecting the retinae of premature infants. Effective screening is necessary for timely treatment. BACKGROUND: The Auckland Regional Telemedicine ROP (ART-ROP) network, utilizes wide-field digital imaging for ROP screening. This study reviews the ART-ROP network. DESIGN: Retrospective analysis of the ART-ROP database. PARTICIPANTS: Files of infants in ART-ROP from 2006 to 2015. METHODS: Data on infant demographics, ROP stage, treatment and outcome was collected. MAIN OUTCOME MEASURES: The efficacy of ART-ROP in the management of ROP. RESULTS: A review of 1181 infants across three neonatal intensive care units, was completed. Infants had a mean of four screening sessions with no infants who met ROP screening criteria being missed. Type 1 ROP was present in 83 infants, who had significantly lower average birth weight 786 ± 191 g compared to 1077 ± 285 g (P < .001), and gestational age 25.3 ± 1.7 weeks compared to 27.8 ± 2.2 weeks (P < .001) than the screened cohort. The number of infants requiring screening increased (R2 = .7993), yet treatment rates decreased (R2 = .9205) across the time period. Out-patient clinic follow-up was attended by 75.10% of infants screened and there was no missed ROP in those infants seen. CONCLUSIONS AND RELEVANCE: ART-ROP solely uses wide-field digital imaging for ROP diagnosis, and management, including discharge, of infants. This detailed review of ART-ROP indicates an increase in screening demand, but a decrease in the rate of type 1 ROP. The ART-ROP telemedicine model demonstrates real potential to address workforce shortage in ROP screening.

Corneal Curvature: the Influence of Corneal Accommodation and Biomechanics on Corneal Shape.

PURPOSE: Variation in the presence and magnitude of corneal conformational changes during accommodation may predict postoperative ectasia following refractive surgery and assist in the early diagnosis of corneal ectatic disorders. The current study aimed to establish a baseline for corneal refractive changes during ocular accommodation and to clarify the role of biomechanical factors in predicting these changes in a population without corneal pathology. METHODS: GALILEI G2 corneal tomography was assessed in 63 participants in both the accommodated and unaccommodated states. Four diopters (D) of physiological accommodation were induced using near-acuity calibrated words viewed through an externally mounted beam splitter mounted on a three-dimensional-printed frame. Corneal biomechanical characteristics were assessed with the CorVis-ST instrument, and statistical analysis was completed in R software. RESULTS: Anterior chamber depth was reduced by 0.10 ± 0.07 mm with accommodation (P < 0.01). Areas of statistically significant change in corneal curvatures were seen in all participants with accommodation. Mean anterior instantaneous corneal power increased in the superior-nasal periphery (0.1 D, 95% confidence interval [CI] = 0.05-0.2 D) and decreased in the inferior-temporal periphery (0.1 D, 95% CI = -0.05 to -0.15 D). Corneal stiffness and the corneal deformation amplitude ratio predicted peripheral corneal curvature changes with accommodation (P < 0.05). CONCLUSION: Corneal conformational changes occur during accommodation in normal subjects. Further studies are required to assess the magnitude of corneal changes during accommodation in patients with corneal ectasia. TRANSLATIONAL RELEVANCE: An externally mounted beam splitter can be used to modify the visual target presented by clinical ocular imaging instruments. Corneal conformational changes during accommodation may be useful in the diagnosis of corneal ectasia.