Dose-Related Visual Outcomes in the Treatment of Choroidal Melanoma with Stereotactic Radiotherapy.

Introduction: Stereotactic radiotherapy (SRT) in the treatment of choroidal melanoma (CM) may be indicated if the tumour is located close to the optic nerve or is unsuitable for a radiotherapeutic plaque. It is thought that the rate of visual decline and ocular sequelae with SRT is influenced by dose and location of radiation in relation to important visual structures. This study therefore aimed to look at these prognoses with respect to localisation and dose of radiation when treatment of CM with SRT occurs. Methods: A retrospective data analysis was conducted on all patients at Dunedin Hospital (DH) from August 2001 to May 2017 who were followed up for 4 years. SRT consisted of 50 Gy divided into five fractions over 5 days to tumours, with 2-mm treatment margins. The primary outcome measure was retention of functional vision - better than hand movements (HMs) within the treated eye. Secondary outcome measures included time to non-functional vision (HM or less) in relation to location, dose and tumour thickness, the presence of radiation retinopathy, local and metastatic tumour progression, enucleation, and disease-specific mortality. Results: Seventy-five patients were identified in this study. Follow-up was incomplete in 10 patients, and 4 patients became deceased within the 4-year study period. Twenty-nine patients (48%) retained visual acuity (VA) better than HMs in the treated eye at 4 years, and thirty-two (52%) of patients did not. Calculated dose to the optic nerve and macula and proximity of the tumour to the optic nerve and macula were not statistically determinative of vision outcomes, although presenting VA was. Fifty-six per cent of patients developed radiation retinopathy involving the macula. The local progression, metastatic progression and enucleation rates were 4.6%, 6%, and 12.3%, representing 3, 4, and 8 patients, respectively. Conclusion: This study demonstrates that approximately half of patients treated with SRT can expect to maintain functional vision better than HM at 4 years. The rate of visual decline and final vision outcome are independent of location of the tumour in relation to the optic nerve and macula. While it affirms that SRT achieves high rates of local tumour control and eye retention, preservation of functional VA remains an unpredictable endpoint for individual cases and highlights the therapeutic challenge of this treatment modality.

The Fight Tumour Blindness Registry: Efficient capture of high-quality real-world data in uveal melanoma.

OBJECTIVE: To describe the development of a web-based data collection tool to track the management and outcomes of uveal melanoma patients. DESIGN: Description of a clinical registry. PARTICIPANTS: Patients with uveal melanoma. METHODS: A panel of expert ocular oncologists, with input from other relevant specialties and individuals with expertise in registry development, collaborated to formulate a minimum data set to be collected to track patient centred, real-world outcomes in uveal melanoma. This data set was used to create the Fight Tumour Blindness! (FTB!) registry within Save Sight Registries. RESULTS: The data set to be collected includes patient demographics and medical history, baseline visit, follow-up visit including tumour treatment, metastatic staging and surveillance, pathology, and patient-reported questionnaires. The inbuilt mechanisms to ensure efficient and complete data collection are described. CONCLUSIONS: The FTB! registry can be used to monitor outcomes for patients with uveal melanoma. It allows benchmarking of outcomes and comparisons between different clinics and countries.

An Overview of the Penguin Visual System.

Penguins require vision that is adequate for both subaerial and submarine environments under a wide range of illumination. Here we provide a structured overview of what is known about their visual system with an emphasis on how and how well they achieve these goals. Amphibious vision is facilitated by a relatively flat cornea, the power in air varying from 10.2 dioptres (D) to 41.3 D depending on the species, and there is good evidence for emmetropia both above and below water. All penguins are trichromats with loss of rhodopsin 2, a nocturnal feature, but only deeper diving penguins have been noted to have pale oil droplets and a preponderance of rods. Conversely, the diurnal, shallow-diving little penguin has a higher ganglion cell density (28,867 cells/mm2) and f-number (3.5) than those that operate in dimmer light. In most species studied, there is some binocular overlap, but this reduces upon submergence. However, gaps in our knowledge remain, particularly with regard to the mechanism of accommodation, spectral transmission, behavioural measurements of visual function in low light, and neural adaptations to low light. The rarer species also deserve more attention.

Confocal and Electron Microscopic Structure of the Cornea from Three Species of Penguin.

Corneal confocal microscopy has not previously been performed in penguins, despite recognition of its unusually flat shape. To identify features that the penguin shares with other birds and or mammals and those specific to penguins, we undertook confocal microscopic examination of two little (Eudyptula minor), four gentoo (Pygoscelis papua) and five king (Aptenodytes patagonicus) penguin corneas. Transmission electron microscopy was performed on one gentoo and one king penguin, for finer details. Features shared with other higher vertebrates included a five-layered cornea and a similar limbus. Typically avian were a lower density of stromal cells, a more regular arrangement of collagen bands and an absent basal nerve plexus. Features unique to penguins included a flattened superficial epithelium (king penguin), stromal myofibroblasts (all) and an irregular endothelium (little penguin). Other features uniquely identified by confocal microscopy in birds include epithelial and stromal nerves, guttata and stromal imprints on Descemet's membrane. Transmission electron microscopy identified a lack of wing cells (king penguin), greater posterior collagen lamellae thickness (gentoo penguin) and significantly less interlacing of collagen lamellae in the central cornea (king and gentoo). Most of these unique features are yet to be explained, but some could be adaptations to diving.

Iris melanocytic tumours in New Zealand/Aotearoa: presentation, management and outcome in a high UV exposure environment.

BACKGROUND/OBJECTIVES: Iris melanoma, a rare intraocular malignancy, represents the smallest subgroup of uveal melanoma. This first, comprehensive study of iris melanocytic lesions in the high ultraviolet environment in New Zealand/ Aotearoa (NZ) examines diagnosis, management and outcomes. SUBJECTS/METHODS: Retrospective study of iris melanocytic tumours referred to tertiary referral centres in Auckland, NZ, over 20 years (1999-2018). Data analysed include demographics, tumour characteristics, histology, genetic analyses, treatment modalities, recurrence, metastasis, 5-year and overall survival. RESULTS: Cohort (N = 51) was predominantly NZ European (98.0%) with no indigenous Maori, or Pasifika. Median age at presentation was 58 years. Tumours involved a median of two clock hours of iris. The posterior tumour margin extended to the anterior chamber angle in 22 patients (45.8%). Management included initial observation 54.9%, iridectomy/excision biopsy 29.4%, irido-cyclectomy 7.8%, plaque radiotherapy 7.8%, proton beam radiotherapy 7.8%, and ultimately enucleation 17.6%. Histology was performed in 19 cases (37%) with 16 confirmed melanomas (84%). Mean follow-up 4.2 years with median visual acuity of 6/7.5 two years post intervention. Melanoma-related metastasis and mortality occurred in two cases with five-year melanoma-related mortality of 2.0%. CONCLUSION: In a climate with high ultraviolet exposure iris melanocytic tumours occurred almost exclusively in NZ Europeans, however, the majority of cases were category T1, possibly reflecting early diagnosis in the NZ health system. Nonetheless, >50% underwent surgery or radiotherapy, often utilising more than one modality. A high index of suspicion and early referral of iris melanocytic lesions should be considered in regions with high UV exposure.

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.

Selective internal radiation therapy for hepatic metastases of uveal melanoma: a systematic review.

OBJECTIVE: Uveal melanoma (UM) commonly metastasizes to the liver. Treatment usually consists of liver-directed therapies, such as selective internal radiation therapy (SIRT). This review aimed to assess the effectiveness and safety of SIRT for hepatic metastases from UM. METHODS: The study protocol is available at OSF (https://osf.io/vhyct/). EMBASE and MEDLINE were searched until July 2020, using terms related to SIRT and hepatic metastases from UM. Studies reporting outcomes of SIRT in patients with UM and at least one hepatic metastasis were included. Data on overall survival (OS), hepatic progression free survival (hPFS) or tumor response were collected. The Newcastle-Ottawa Scale (NOS) was used to assess risk of bias. RESULTS: 11 studies were included, reporting outcomes for 268 patients with hepatic metastases from UM. Most studies (n = 9, 81.8%) were retrospective. Disease control was achieved in 170 patients (67.5%) and the median OS from time of SIRT was 12.3 months. Median hPFS was 5.4 months. Low-grade side-effects were common but serious complications were infrequent. There were two treatment-related deaths. The median NOS score was 6 (moderate risk of bias). CONCLUSION: SIRT appears to be a safe and effective treatment for patients with unresectable hepatic metastases from UM. The certainty of our results is unclear due to predominantly retrospective data with moderate risk of bias. Further prospective studies are required to explore the role of SIRT in UM. ADVANCES IN KNOWLEDGE: SIRT appears to be a safe treatment for patients with unresectable hepatic metastases from UM. Further prospective work is required.

Micro-CT guided illustration of the head anatomy of penguins (Aves: Sphenisciformes: Spheniscidae).

The illustration is an important tool to aid in the description and understanding of anatomy, and penguins (Aves: Sphenisciformes: Spheniscidae) are an important clade in environmental monitoring, paleontology, and other research fields. Traditionally, anatomic illustration has been informed by dissection. More recently, micro-computed tomography (micro-CT) has proven to be a powerful tool for three-dimensional anatomic imaging, although larger specimens are more challenging to image due to increased X-ray attenuation. Here, we used traditional dissection and micro-CT to illustrate the skulls of Aptenodytes patagonicus, Eudyptula minor, and Pygoscelis papua, and the extracranial soft tissue of E. minor. Micro-CT prevented the loss of orientation, disarticulation, and distortion of bones that might result from cleaning and drying skulls, while immobilization was achieved by freezing the specimens before imaging. All bony elements in the head were accurately depicted. Fixing, dehydrating, and diffusion staining with iodine (diceCT) enabled the identification of muscles and other large nonmineralized structures, but specimen preparation precluded the ability to show smaller nerves and vessels. The results presented here provide a guide for anatomic studies of penguins and our summary of sample preparation and imaging techniques are applicable for studies of other similarly sized biological specimens.

Selected ocular dimensions of three penguin species.

Penguins (Spheniscidae) are a diverse clade of flightless, marine birds. Their eyes, likely a primary driver of behaviour, have been noted to have anatomic adaptations to their amphibious lifestyle. In particular, they have a relatively flat cornea, which would make the transition from a subaerial to a submarine environment require less accommodative effort. However, the ocular dimensions are not known for many penguin species, despite the diversity within the family, and their accommodative abilities have been the source of some dispute. In this study we undertook to establish the basic dimensions of the eye of the smallest, a mid-sized penguin and the second largest penguin. The power of the front surface of the cornea was inversely related to the size of both the eye and penguin, being 41.3 D in the little penguin (Eudyptula minor), a power greater than previously measured in any other penguin species, 26.3 D in the gentoo (Pygoscelis papua) and 19.1 D in the king penguin (Aptenodytes patagonicus). All other dimensions increased or decreased in line with the size of the eye. All penguins were able to achieve emmetropia in air. The gentoo appeared to be emmetropic underwater. A finding of central corneal thickening in some penguins may be artefactual. Calculations using the ocular dimensions demonstrated that the mean retinal illumination of an extended source of light in the little penguin eye is less than that of its larger, deeper-diving relatives.

Genomic insights into the secondary aquatic transition of penguins.

Penguins lost the ability to fly more than 60 million years ago, subsequently evolving a hyper-specialized marine body plan. Within the framework of a genome-scale, fossil-inclusive phylogeny, we identify key geological events that shaped penguin diversification and genomic signatures consistent with widespread refugia/recolonization during major climate oscillations. We further identify a suite of genes potentially underpinning adaptations related to thermoregulation, oxygenation, diving, vision, diet, immunity and body size, which might have facilitated their remarkable secondary transition to an aquatic ecology. Our analyses indicate that penguins and their sister group (Procellariiformes) have the lowest evolutionary rates yet detected in birds. Together, these findings help improve our understanding of how penguins have transitioned to the marine environment, successfully colonizing some of the most extreme environments on Earth.

Vitreoretinal fellow surgical outcome of small gauge pars plana vitrectomy for acute rhegmatogenous retinal detachment.

BACKGROUND: Our purpose was to determine the anatomical outcome following small gauge vitrectomy for acute rhegmatogenous retinal detachment (RRD) operated by vitreoretinal fellows. METHODS: We undertook a retrospective review of adult patients presenting with an acute RRD treated with small gauge vitrectomy where the operating surgeon was either a vitreoretinal fellow or consultant surgeon. The patient's demographics were recorded as well as relevant clinical findings. The end point was determined to be the anatomical outcome and number of surgeries. RESULTS: Two hundred and twelve eyes were included in this study. The age range was 21-90 years, with approximately one third of the patients being female. The macula was attached in 53% at presentation, and 65% of the eyes were phakic. Primary re-attachment with a single operation was achieved in 75% of cases, and final re-attachment rate was 92%. Mean presenting visual acuity was LogMAR 1.07 (SD 1.09) and final visual acuity was LogMAR 0.63 (SD 0.85). We found no association between final anatomical success and experience of the surgeon (p = 0.6). CONCLUSION: We found that acute RRD treated by vitreoretinal fellows using small gauge vitrectomy did not place the patient at any discernable disadvantage.

Impact of the COVID-19 pandemic lockdown on public sector ophthalmic work by New Zealand's ophthalmologists.

AIM: In response to the COVID-19 pandemic, the New Zealand government enforced a nationwide 'alert level 4' lockdown from 26 March to 27 April 2020. We assessed the impact of this lockdown on New Zealand's public ophthalmology service. METHOD: An anonymous online survey was sent to all New Zealand-based fellows of the Royal Australian and New Zealand College of Ophthalmologists (RANZCO) after lockdown. Respondents provided retrospective assessment of practice patterns and their personal health during the COVID-19 lockdown. This was supported by national-level administrative data, allowing survey findings to be contextualised. RESULTS: Fifty-seven respondents (response rate 49%) working in the public health system participated. A large majority of respondents reduced elective clinic and surgical volumes by at least 75% (82% and 98%, respectively). National-level information confirmed clinic reduced to 38.2% of normal and elective operating volumes to 11.5%, with virtual visits increasing 17.9-fold. Elective clinic and elective operating volumes promptly recovered to usual volumes on the second month post lockdown. Most respondents (58%) followed the RANZCO triaging guideline, and 28% triaged emergencies only. At a personal level, respondents reported a significant physical health benefit (p<0.001) associated with the lockdown experience, but no change in mental health or social wellbeing. CONCLUSIONS: Publicly employed ophthalmologists experienced dramatic reductions to elective clinic and operating volumes during the COVID-19 lockdown. The prompt recovery of service delivery volumes back to pre-lockdown levels supports the value of a COVID-19 elimination strategy in New Zealand. Virtual visits for selected patients allowed ongoing management without risking virus transmission.

Skeletal elements of the penguin eye and their functional and phylogenetic implications (Aves: Sphenisciformes: Spheniscidae).

Scleral ossicles and other bony elements are present in the eyes of many vertebrates, including birds. In this study, the skeletal elements present in the penguin eye and orbit were imaged using macro photographs and micro-computed tomography (micro-CT), to help elucidate their function and significance. A total of 36 scleral rings and three whole skulls were imaged. King (Aptenodytes patagonicus), Fiordland crested (Eudyptes pachyrhynchus), Snares crested (Eudyptes robustus), royal (Eudyptes schlegeli) and yellow-eyed (Megadyptes antipodes) penguins had between 12 and 14 elements in their scleral ring while the gentoo (Pygoscelis papua) had 14 and 17; little penguins (Eudyptula sp.) consistently had between 10 and 12 elements. All had at least two elements that overlapped, usually totally, each neighbour, and two that were overlapped by each neighbour. The interior structure of all ossicles revealed a lattice-like arrangement of struts typical of cancellous bone, the whole being surrounded by thick cortical bone. The scleral ring of a 10 week gentoo chick was not completely ossified but rather had multiple small holes within it on micro-CT. A large os opticus was present in one king penguin but in another bird of the same age and gender there was no such bone. Much smaller accessory bones were found in the posterior pole of one Snares crested and one little penguin. We conclude that the penguin scleral ring not only maintains the shape of the eye but also provides protection and a site of insertion for rectus muscles. However, the extreme variability in the os opticus suggests that it is not essential to normal function.

Consecutive choroidal melanoma in the same eye of a patient.

PURPOSE: To report the occurrence of two entirely separate choroidal melanomas in the same eye of one patient. DESIGN: Observational case report. METHODS: Retrospective case report from one clinical practice. Two choroidal melanomas were observed to develop in the same eye of one patient. RESULTS: An inferonasal choroidal melanoma was diagnosed in the left eye of a 30-year-old woman in 1990. This was successfully treated with proton beam radiotherapy. In 1996, a superotemporal choroidal tumor in the same eye was observed to grow rapidly and it was treated with a ruthenium plaque in 1996. There was a history of cutaneous malignant melanoma. CONCLUSIONS: It is extremely rare for two choroidal melanomas to develop in one eye, and there may be a genetic predisposition.