Cysts and tumours of the iris: Diagnostic tools and key management considerations-A review.

The iris is a unique structure, with exquisite variations in colour and form. Pathological changes, specifically including iris cysts and tumours are relatively uncommon, difficult to diagnose, and yet potentially blinding or life-threatening. Based on a comprehensive literature review, with highly illustrated key case examples, this report aims to guide the clinician in filtering the differential diagnoses of iris cysts and tumours. Evaluation is in the context of key diagnostic clinical tools and management considerations. Diagnostic imaging techniques include serial anterior segment photography, ultrasound, anterior segment optical coherence tomography, and iris fluorescein angiography, however, the roles of computerised topography and magnetic resonance imaging are also considered in this review. Management includes categorisation in terms of solid iris tumours (melanocytic vs. non-melanocytic), or iris cysts (primary vs. secondary) that may be usefully differentiated by clinical assessment, avoiding more invasive interventions. Cystic lesions are generally benign, although implantation cysts in particular cause significant complications and surgical challenges. Most solid tumours are melanocytic and also typically benign. However, in larger lesions, rapid growth, symptoms and complications more likely indicate malignancy, requiring further investigation.

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.

Tumor Profiles of Late Presentation Uveal Ring Melanoma With Novel Characteristics - A Case Series.

Purpose: The purpose of this study was to investigate the clinical features, tumor characteristics, including histopathology and cytogenetic analysis, and management of patients with uveal ring melanoma in New Zealand. Methods: A retrospective review was conducted on all uveal melanoma cases treated in a single national oncology center in New Zealand. The study period was from January 1, 2013 to December 31, 2022 (10 years). Written consent was obtained from all patients included in this case series. Results: Uveal ring melanoma of ciliary body origin (n = 4) comprised 0.7% of all uveal melanomas (n = 571). Ethnicity distribution was three patients of New Zealand European ancestry and one patient of Chinese/Pasifika ancestry. Three patients (75%) were symptomatic at presentation (spontaneous hyphema, glaucoma, and cataract), whereas one was asymptomatic but subsequently developed painful refractory glaucoma. All eyes underwent enucleation. Three eyes had primary iris biopsies with subsequent enucleation for refractory glaucoma and pain and one eye underwent primary enucleation. All cases demonstrated malignant tumor characteristics including diffuse 270 to 360-degree ciliary body ring growth pattern, epithelioid-cell type and presence of either BAP-1 expression loss or gain of MYC gene. Two cases (50%) developed distant organ metastasis - liver, parotid gland, and breast. Of those, one patient was deceased at the time of follow-up whereas one had completed treatment for metastases. Conclusions: Uveal ring melanoma is a rare tumor that is highly invasive and malignant. When detected, prompt definitive treatment should be advocated, and patient counselling should be given regarding the high risk of developing a painful, blind eye with increased risk of metastasis in the absence of treatment.

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.

Endocapsular artificial iris implantation for iris defects: Reducing symptoms, restoring visual function and improving cosmesis.

BACKGROUND: To investigate repair of iris defects by endocapsular implantation of an artificial iris, in relation to visual outcomes, safety profile and patient satisfaction. METHODS: Retrospective, consecutive case series from Greenlane tertiary teaching hospital and Eye Institute, Auckland, New Zealand. Medical records of patients implanted with an endocapsular artificial iris were reviewed and followed for minimum 3 months. Patient characteristics, surgical management, clinical outcomes and subjective responses were recorded. RESULTS: Nineteen artificial irises were implanted in 18 patients. Etiologies were iris melanotic lesion excision (73.7%), trauma (10.5%), congenital aniridia (10.5%) and Urrets-Zavalia syndrome (5.3%). During postoperative follow-up [14.1 ± 12.4 months (range: 3 to 59 months)], best corrected visual acuity (BCVA) and intraocular pressure (IOP) did not change significantly [BCVA, 0.23 logarithm of the minimum angle of resolution (logMAR) (20/32 Snellen) preoperatively vs. 0.18 logMAR postoperatively (20/25 Snellen) (Z = -0.222, p = 0.824); IOP, 15 mmHg preoperatively vs. 17 mmHg postoperatively (Z = 1.377, p = 0.1447)]. Mild or self-limiting complications included: elevated IOP (42.1%), cystoid macular oedema (15.8%); persisting postoperative uveitis (15.8%) and minor vaulting of the prosthesis (15.7%). Moderate or severe complications included significant vaulting of prosthesis requiring surgical revision (5.3%) and a single eye (5.3%) with trabeculectomy and corneal graft failure. 94.4% of patients were very satisfied with the cosmesis and would be highly likely to have the procedure again. CONCLUSIONS: This study confirms that endocapsular insertion of an artificial iris is typically associated with good functional and cosmetic results and a relatively low risk of significant complications.

Evaluating the diagnostic ability of two automated non-invasive tear film stability measurement techniques.

PURPOSE: To evaluate the comparability, discriminative ability, and optimal thresholds for non-invasive tear film breakup time measurements obtained from the Oculus Keratograph 5M and Medmont E300 in detecting other signs and symptoms of dry eye disease, as defined by the TFOS DEWS II diagnostic criteria. METHODS: One hundred and thirty-four participants (53 male, 81 female), with a mean ± SD age of 48 ± 20 years, were recruited into a prospective, investigator-masked, diagnostic accuracy study. Dry eye symptomology, tear film parameters (including non-invasive Keratograph and Medmont breakup time), and ocular surface staining were evaluated in a single clinical session. RESULTS: Significant positive correlation was observed between the two automated instruments (p < 0.001), although non-invasive breakup time measurements obtained from the Medmont were significantly longer (p < 0.001), and demonstrated greater intra-subject and inter-subject variability (all p < 0.001). The areas under the ROC curves exceeded 0.65 for both instruments, and the discriminative abilities were comparable (p = 0.53). The Youden optimal diagnostic threshold for non-invasive tear film stability measurements obtained from the Keratograph was ≤8 seconds, and the optimal cut-off for breakup time measurements obtained from the Medmont was ≤14 seconds. CONCLUSIONS: Despite significant positive correlation, breakup time measurements obtained from the Keratograph and Medmont were not directly interchangeable. Measurements from the Medmont were significantly longer and demonstrated greater intra-subject and inter-subject variability, although the two automated, non-invasive methods for assessing tear film stability exhibited comparable overall performance in diagnosing dry eye disease.

Ageing and the natural history of dry eye disease: A prospective registry-based cross-sectional study.

PURPOSE: To investigate the impact of ageing on ocular surface parameters, and empirically determine optimal prognostic cut-off ages for clinical markers of dry eye disease, aqueous tear deficiency, and meibomian gland dysfunction. METHODS: A total of 1331 community residents (785 females, 546 males; mean ± SD age, 38 ± 19 years) were recruited in a prospective registry-based cross-sectional study. Dry eye symptomology, ocular surface characteristics, and tear film quality were evaluated for each participant within a single clinical session, in accordance with the global consensus recommendations of the TFOS DEWS II reports. RESULTS: Multivariate regression analysis demonstrated positive associations between ageing and clinical markers of dry eye disease (all p ≤ 0.001). The Youden-optimal prognostic cut-off ages for signs of meibomian gland dysfunction occurred during the third decade of life (24-29 years); the optimal predictive ages for lid wiper epitheliopathy, tear film instability, hyperosmolarity, and dry eye symptoms occurred during the fourth decade of life (31-38 years); while the optimal prognostic thresholds for signs of aqueous tear deficiency and ocular surface staining occurred in the fifth and sixth decades of life (46-52 years). CONCLUSIONS: Advancing age is a significant risk factor for dry eye disease, which represents a growing public health concern with the ageing population worldwide. Signs of meibomian gland dysfunction appeared earlier in the natural history of disease progression, and the brief delay prior to the development of other clinical dry eye signs might represent a window of opportunity for preventative interventions in the young adult age group.

Effect of Diabetes Mellitus on Cardiac Resynchronization Therapy and to Prognosis in Heart Failure (from the Prospective Evaluation of Asian With Cardiac Resynchronization Therapy for Heart Failure Study).

The association of diabetes mellitus (DM) with cardiac resynchronization therapy (CRT) response and cardiovascular outcomes in Asian patients with heart failure (HF) is unclear. This study aims to investigate the effects of DM on CRT response and cardiovascular outcomes in Asian HF patients. Consecutive Asian HF patients receiving CRT were enrolled in the Prospective Evaluation of Asian with CRT for Heart Failure (PEACH) study from 2011 to 2017. CRT response and super-response were defined as decrease in end-systolic volume index ≥15% and ≥30%, respectively. Primary endpoint was time to composite of HF-hospitalization and all-cause mortality. Among 161 patients followed for 3.3 ± 1.5 years (age 66.7 ± 11.2 years, 22% females, mean QRS duration 154.3 ± 22.4 ms, 83% left bundle branch block), 84 (52%) were CRT responders and 57 (35%) were super-responders. Of 82 (51%) patients with DM (100% type 2, mean HbA1c 7.3 ± 1.9%), 35 (43%) were responders. DM attenuated reverse remodeling (CRT response: AOR 0.44, 95% confidence interval [CI] 0.20 to 0.98, p < 0.05; super-response: AOR 0.42, 95% CI 0.18 to 0.97, p <0.05), and DM increased HF-hospitalization and all-cause mortality (AHR 1.68, 95% CI 1.00 to 2.82, p = 0.05). The extent of CRT-response correlates with higher event-free survival (CRT response: AHR 0.5, 95% CI 0.30 to 0.81, p = 0.005; super-response: AHR 0.27, 95% CI 0.14 to 0.52, p < 0.001). In conclusion, the extent of reverse remodeling post-CRT is the strongest predictor of event free survival. However, DM is detrimental to the CRT recipient by attenuating reverse remodeling, inducing end organ dysfunction and is independently associated with worsened clinical outcomes among Asian HF patients.

Ethnic differences between the Asian and Caucasian ocular surface: A co-located adult migrant population cohort study.

PURPOSE: To investigate the ethnic differences in tear film quality, ocular surface parameters, and dry eye symptomology between co-located Asian and Caucasian populations. METHODS: Two hundred and six participants (103 East Asian and 103 Caucasian) were recruited in an age and gender-matched cross-sectional study. Dry eye symptomology, ocular surface parameters, and tear film quality were evaluated for each participant within a single clinical session. RESULTS: The mean ±â€¯SD age of the 206 participants (82 male, 124 female) was 45 ±â€¯16 years. Overall, a greater proportion of Asian participants were symptomatic of dry eye and fulfilled the TFOS DEWS II dry eye diagnostic criteria than Caucasian participants (74% versus 51%, p = 0.002), with an odds ratio (95% CI) of 2.7 (1.5-4.8) times. Poorer OSDI scores, tear film stability, lipid layer quality, tear osmolarity, lid wiper epitheliopathy, meibomian gland dropout, and expressed meibum quality were observed in the Asian group (all p < 0.05). A significantly higher proportion of participants exhibited incomplete blinking in the Asian group than the Caucasian group (81% versus 45%, p < 0.001). CONCLUSIONS: Asian participants exhibited more severe dry eye signs and symptoms than Caucasian participants. The poorer meibomian gland function and higher degree of incomplete blinking observed among Asian participants may potentially contribute towards the ethnic predisposition towards dry eye development.

Minimising instilled volume reduces the impact of fluorescein on clinical measurements of tear film stability.

PURPOSE: To compare clinical tear film break-up time measurements obtained non-invasively, with those measured following minimal and conventional volumes of fluorescein instillation. METHODS: Forty-one subjects (20 male, 21 female, mean±SD age 34±11years), with or without dry eye, participated in a prospective cross-over study. Tear film break-up time was measured by the Tearscope Plus™ with fine grid insert. Measurements were made in triplicate, with no fluorescein instillation (NIBUT), then following application of a minimal volume of 1µl fluorescein from the Dry Eye Test™ (mTBUT), and finally with 15-30µl of fluid instilled via a conventional fluorescein strip (TBUT). A fifteen-minute interval between each set of measurements minimised the risk of residual contamination effects. RESULTS: All three techniques displayed statistically significant pairwise correlation (all p<0.001). TBUT values were significantly shorter than both NIBUT (geometric mean 8.6s versus 10.9s, p=0.03) and mTBUT (geometric mean 8.6s versus 10.6s, p=0.03), and demonstrated narrower spread (both p<0.05). No significant differences were detected between NIBUT and mTBUT (all p>0.05). CONCLUSIONS: Tear film break-up time values measured with conventional fluorescein instillation were shortened, while minimal fluorescein instillation and non-invasive methods produced comparable readings. This suggests that minimising instilled volumes can reduce the impact of fluorescein on clinical measurements of tear film stability.