When Is the Optimum Radiological Response to Proton Beam Therapy in Uveal Melanoma?

Introduction: Proton beam therapy (PBT) is an effective treatment option for uveal melanomas. Following treatment, it may take many months for the tumour to respond and it may initially enlarge. We reviewed our PBT patients to determine when they showed a radiological response to treatment. Methods: Patients undergoing PBT for ciliary body or choroidal melanomas between 2008 and 2018 were included. Data were collected on patient demographics, treatments before and after PBT and survival. All ultrasound investigations prior and since PBT were reviewed and tumour volume calculated using a validated formula for a half-ellipsoid shape. Results: 193 patients were analysed, 169 with choroidal and 24 with ciliary body melanomas. 31.6% patients had other treatment prior to PBT. At a mean of 8 months post-PBT, 64.7% of patients had a reduced tumour volume with 20.2% having larger tumours. At a mean of 15 months post-treatment, these figures were 67.8% and 10.3%. 18.1% of patients had an enucleation during the study period. The earliest responses were seen at 2 months, the latest at 32 months post-treatment. 5-year melanoma-specific survival was 82.3%. Conclusions: In our study, by 6 months post-PBT, a majority of patients show a reduction in tumour volume. Of those that do not, many respond in the next 6 months and a response may be seen up to 32 months after treatment. Patients may need to be monitored for up to 32 months to see a final response to PBT treatment.

Is an image-based eyelid management service safe and effective?

INTRODUCTION: The COVID-19 pandemic created a requirement for reduced patient contact and reduced capacity in clinics. We previously published results of an Image-Based Eyelid Lesion Management Service (IBELMS) which was found non-inferior to traditional face-to-face clinic at diagnosing lesions and identifying eyelid malignancies. We now present first-year safety and efficacy data from this service. METHODS: Data were collected retrospectively on all patients seen in NHS Greater Glasgow and Clyde eyelid photography clinics from 30th September 2020 to 29th September 2021, including referral source and diagnosis, time to clinic review, treatment and patient outcomes. RESULTS: 808 patients were included in the study. Chalazion was the most common diagnoses recorded (38.4%). There was a statistically significant decrease in mean time from referral to appointment time between the first 4 months and last 4 months of the service (93 days to 22 days, p ≤ 0.0001). 266 (33%) of patients were discharged following photographs, 45 (6%) were discharged for non-attendance and 371 (46%) were booked for a minor procedure. 13 biopsy-confirmed malignant lesions were identified; only 3 had been referred as suspected malignancy. 23 patients out of 330 with at least 6 months follow up (7%) were re-referred within 6 months of treatment or discharge; however, none of them with a missed periocular malignancy. DISCUSSION: Eyelid photography clinics effectively reduce patient waiting times and maximise clinic capacity. They accurately identify eyelid lesions including malignancies with a low re-referral rate. We propose that an image-based service for eyelid lesions is a safe and effective way of managing such patients.

Multicenter Evaluation of Pre-operative Feeding in Infants with Ductal Dependent Circulation.

Enteral feeds are often withheld from neonates with ductal dependent cardiac lesions who are receiving prostaglandins. This is despite positive benefits of enteral feeding. We describe a multicenter cohort of these neonates who were fed pre-operatively. We also give a granular description of vital sign measurements and other risk factors prior to feeding. A retrospective chart review was performed at seven centers. Inclusion criteria were full-term neonates under one month of age with ductal dependent lesions receiving prostaglandins. These neonates were fed for at least 24 h during the pre-operative period. Premature neonates were excluded. Using the inclusion criteria, 127 neonates were identified. While being fed, 20.5% of the neonates were intubated, 10.2% were on inotropes, and 55.9% had an umbilical arterial catheter in place. Median oxygen saturations in the six hours prior to feeding were 92.5% in patients with cyanotic lesions, median diastolic blood pressure was 38 mmHg and median somatic NIRS were 66.5%. The median peak daily feeding volume reached was 29 ml/kg/day (IQ range 15.5-96.8 ml/kg/day). One patient developed suspected necrotizing enterocolitis (NEC) in this cohort. Only one adverse event occurred, which was an aspiration thought to be related to feeding, but did not result in intubation or cessation of feeds. NEC was rare among neonates with ductal dependent lesions while receiving enteral nutrition pre-operatively. Umbilical arterial catheters were in place in the majority of these patients. Hemodynamic measures demonstrated a high median oxygen saturation prior to initiation of feeds.

Post-enucleation outcomes of patients with uveal melanoma in Scotland.

BACKGROUND/OBJECTIVES: To investigate post-enucleation outcomes and assess the effect of extrascleral extension (ESE) on these outcomes for patients with uveal melanoma (UM) managed at a tertiary referral centre in Scotland. SUBJECTS/METHODS: Retrospective review of all cases of UM managed by the Scottish Ocular Oncology Service for which enucleation was undertaken between 13/03/2008 and 31/12/2020. Primary outcomes were length of survival, time-to-metastasis (TTM) and local recurrence rate. Secondary outcomes were the effects of the presence of ESE, ESE size, and the use of adjuvant external beam radiotherapy (EBRT) on the primary outcomes. RESULTS: Of 172 enucleated UMs, 32 (18.6%) had ESE. Over a median follow-up period of 33.7 months (range = 1.1-163.7 months), 91 (52.9%) patients died. The median length of all-cause survival of 54.1 months (range = 1.1-163.7 months). One-year, 5-year, and 10-year survival rates were 84.8%, 49.1%, and 30.9%, respectively. Eighty-four (49.7%) patients had metastatic disease. The median TTM of 42.2 months (range = 0.4-106.8 months). Proportions of patients who developed metastases within 1-year, 5-years and 10-years post-enucleation were 22.7%, 52.8%, and 71.8%, respectively. There was one instance of local orbital recurrence. ESE was associated with a significantly shorter length of survival (p = 0.03). There was a trend towards a shorter length of survival and TTM with ESE > 5 mm and those who received adjuvant EBRT. CONCLUSIONS: ESE was present in one-sixth of our cohort and was associated with a significantly shorter length of survival, particularly in the presence of ESE > 5 mm or high-risk characteristics warranting adjuvant EBRT. This data will aid prognostication of the patients in our service.

Outcomes of cataract surgery in patients previously treated with orbital radiotherapy.

PURPOSE: To quantify the risks for cataract surgery in patients who have previously undergone external beam radiotherapy (EBRT). SETTING: Tertiary ophthalmology and oncology hospital. DESIGN: Retrospective case series. METHODS: Patients treated with orbital EBRT at the Beatson West of Scotland Cancer Centre between 2001 and 2019 were identified, and clinical records were reviewed to identify those who had subsequently undergone cataract surgery. Preoperative and postoperative case records, and operation records, were reviewed to identify demographic data and data regarding complications and surgical outcomes. RESULTS: 46 eyes (of 33 patients) were included. The indications for EBRT included thyroid eye disease, lymphoma, choroidal metastases, and other orbital malignancies. Mean corrected preoperative Snellen visual acuity was 20/100 (range 20/30 to 20/2000) improving to 20/25 (20/12 to 20/160, 1-way analysis of variance P < .01). Mean visual gain was 0.5 logMAR (-0.9 to 1.9). There was 1 case of posterior capsule (PC) rupture with vitreous loss (2%). Dense PC plaque was noted intraoperatively in 19.5% (n = 9). 13% (n = 6) required Nd:YAG laser posterior capsulotomy. There were 6 cases (13%) of cystoid macular edema (CME). CONCLUSIONS: Visual outcomes after cataract surgery in this cohort of patients were similar to those obtained in a nationwide cohort. EBRT seemed to be associated with an increased incidence of intraoperative PC plaque, postoperative CME (which in most cases settled with treatment), and need for posterior capsulotomy.

Impact of COVID-19 pandemic on eye cancer care in United Kingdom.

The COVID-19 pandemic has had an unprecedented impact on the National Health Service in United Kingdom. The UK Ocular Oncology Services evaluated the impact on the adult eye cancer care in the UK. All four adult Ocular Oncology centres participated in a multicentre retrospective review comparing uveal melanoma referral patterns and treatments in a 4-month period during the national lockdown and first wave of the COVID-19 pandemic in 2020 with corresponding periods in previous 2 years. During the national lockdown, referral numbers and confirmed uveal melanoma cases reduced considerably, equalling to ~120 fewer diagnosed uveal melanoma cases compared to previous 2 years. Contrary to the recent trend, increased caseloads of enucleation and stereotactic radiosurgery (p > 0.05), in comparison to fewer proton beam therapy (p < 0.05), were performed. In the 4-month period following lockdown, there was a surge in clinical activities with more advanced diseases (p < 0.05) presenting to the services. As the COVID-19 pandemic continues to mount pressure and reveal its hidden impact on the eye cancer care, it is imperative for the Ocular Oncology Services to plan recovery strategies and innovative ways of working.

Outcomes following Notched Ruthenium-106 Plaque Brachytherapy for Juxtapapillary Choroidal Melanomas.

PURPOSE: This study aimed to evaluate the outcomes of juxtapapillary choroidal melanomas treated with notched ruthenium-106 plaques. METHODS: Juxtapapillary choroidal melanomas (tumours within 2 disc diameters from the optic disc) treated with notched ruthenium-106 plaques (Eckert & Ziegler, BEBIG, Berlin, Germany) at the Scottish Ocular Oncology Service between 2009 and 2015 were retrospectively reviewed. The data were analysed with respect to various outcome measures including recurrence, complications, vision, and eye preservation. RESULTS: We reviewed 40 patients with a median tumour diameter of 8.4 mm (range 5-17 mm) and a median thickness of 2.5 mm (range 1.1-6 mm). AJCC tumour category distribution was 62.5% T1, 32.5% T2, and 5% T3 tumours. The mean presenting vision was 0.3 logMAR, and the mean final vision was 0.7 logMAR, with 62.5% retaining >1.0 logMAR and 50% retaining >0.3 logMAR at the final follow-up. The median follow-up was 51 months (14-100 months). Over the maximum follow-up time, 13 tumours (32.5%) recurred. Six of these were treated with salvage proton beam therapy (PBT), 2 with transpupillary thermotherapy followed by PBT, and 5 with enucleation. The final eye retention rate was 87.5%. Complications included maculopathy (10%), retinal detachment (5%), neovascular glaucoma (2.5%), and diplopia (2.5%). The observed risk of recurrence over 5 years was 31% (95% CI: 14.1%, 47.8%), and the risk of enucleation over 5 years was 11.5% (95% CI: 0.9%, 21.8%). CONCLUSION: Juxtapapillary choroidal melanomas treated with notched ruthenium plaques have a high recurrence rate and frequently need salvage treatment with PBT for tumour control. This has led to a change in our practice toward offering PBT as the first-line treatment for these patients.

A refractive optical device potentially masking an intraocular tumor.

A 62-year-old woman was referred with reduced vision in her left eye and suspected retinal detachment. Bilateral laser in situ keratomileusis with KAMRA corneal inlay insertion was performed in the left eye 2 years earlier. On examination, a shadow from the corneal inlay limited posterior segment examination even with dilated fundoscopy, but a temporal raised lesion extending over the macula was noted. Ocular ultrasound confirmed a large tumor consistent with malignant melanoma, requiring enucleation. It is unclear whether the patient had baseline dilated fundoscopy before corneal inlay implantation; however, a pinhole effect for the patient will cause a pinhole effect for the clinician, potentially limiting the fundal view. The authors emphasize the importance of appropriate informed consent patients, including discussion of rare risks and complications, which can have profound implications. In this case, the elective refractive procedure potentially masked an intraocular tumor. Enucleation may have been avoided if the lesion had been identified at an earlier stage.

Multifocal Intraretinal Tumour Deposits following Treatment of an Ipsilateral Choroidal Melanoma.

BACKGROUND/AIMS: The aim of this study was to report a patient who, following plaque brachytherapy for a choroidal melanoma, developed two separate retinal foci of malignant melanoma in the same eye, and suggest possible mechanisms that might explain such an occurrence. METHODS: We conducted a retrospective case report. RESULTS: A 79-year-old Caucasian male developed a left inferotemporal choroidal melanoma in 2016 and subsequently underwent ruthenium-106 plaque brachytherapy under the care of the Scottish Ocular Oncology Service. Serial B-scan ultrasonography demonstrated a post-treatment reduction in tumour height to <2 mm. In 2018, 27 months after the treatment, the patient complained of a "black spot" in the centre of his left eye vision. His visual acuity had reduced to counting fingers from 6/24 (corrected Snellen visual acuity). Several new areas of pigmentation and elevation were observed, and uveal melanoma recurrence was initially suspected. Given the multifocal nature of the presentation, the multi-disciplinary team recommended enucleation. Histological examination of the enucleated eye revealed three discrete foci of malignant melanoma - the previously treated choroidal malignant melanoma, and two solitary deposits of malignant melanoma within the retina. CONCLUSION: Retinoinvasive melanoma is a rare subtype of uveal melanoma, characterised by transvitreal melanoma invasion of the retina at a site non-contiguous with the uveal tumour, which may explain the clinical and pathological findings of the reported case.

Impact of connective tissue graft thickness on surgical outcomes: A pilot randomized clinical trial.

BACKGROUND: The aim of this study was to compare thick versus thin connective tissue grafts (CTG) for the treatment of gingival recession, over a 3-month period. METHODS: Forty-two CTG procedures were performed on single tooth Miller Class I or II recession defects at either premolar or anterior sites in 30 individuals. Procedures were randomized (1:1 ratio) to CTG thickness of 1 or 2 mm (parallel group design). Primary outcomes were the change in the width of the zone of keratinized tissue and the amount of root coverage achieved 3 months postoperatively at the recipient site. Secondary outcomes included change in the thickness of keratinized tissue at 3 months and patient-reported outcomes, such as pain, bleeding, and swelling at both the recipient and donor sites at 1 week, 2 weeks, 1 month, and 3 months. RESULTS: No significant differences were found between the two groups for any of the primary or secondary outcomes. Mean root coverage achieved was 2.1 ± 0.2 mm in the 1-mm thick group and 2.5 ± 0.2 mm in the 2-mm thick group (P = 0.33). Keratinized tissue width was increased by 2.2 ± 0.2 mm in the 1-mm thick group and by 2.7 ± 0.3 mm in the 2-mm thick group (P = 0.18). Keratinized tissue thickness was increased by 1.0 ± 0.1 mm and by 1.2 ± 0.1 mm in the 1- and 2-mm thick groups, respectively (P = 0.09). CONCLUSION: Within the current study limitations, our results suggest that similar root coverage and increase in the width and thickness of keratinized tissue can be achieved at 3 months whether a 1- or 2-mm thick CTG is used.

Prescribing lessons from an ocular chemical injury: Vitaros inadvertently dispensed instead of VitA-POS.

We wish to report an ocular chemical injury caused by inadvertent dispensing and administration of an erectile dysfunction cream (Vitaros) instead of an ocular lubricant (VitA-POS) to highlight this potential source of error. Prescribing errors are common, and medications with similar names/packaging increase risk. However, it is unusual in this case that no individual (including the patient, general practitioner or dispensing pharmacist) questioned erectile dysfunction cream being prescribed to a female patient, with ocular application instructions. The patient was treated for a mild ocular chemical injury with topical antibiotics, steroids and lubricants, with good response. However, we believe this to be an important issue to report to enhance awareness and promote safe prescribing skills.

Pharmacokinetics of intravitreal anti-VEGF drugs in vitrectomized versus non-vitrectomized eyes.

INTRODUCTION: The review aims to discuss effects of vitrectomy on pharmacokinetics of anti-vascular endothelial growth factor (anti-VEGF) agents, and attempt to provide treatment guidance. Areas covered: An Embase search was conducted using the terms 'anti-VEGF', 'pegaptanib', 'ranibizumab', 'bevacizumab', 'aflibercept', 'pharmacokinetics', 'half-life', 'clearance', 'metabolism', 'vitrectomy', 'vitrectomized'. Published data regarding the pharmacokinetic properties of the above drugs and the effect of vitrectomy in animal and human eyes was reviewed. Expert opinion: There are limited studies on the effect of vitrectomy on pharmacokinetic properties of anti-VEGF drugs in human eyes. Most animal models indicate that intravitreal drugs have reduced half-lives and increased clearance in vitrectomized eyes. More studies, with carefully selected design, are required to explore this further. However, considering existing evidence, it is important to consider vitreous and lens status when monitoring and treating patients. Authors recommend fixed monthly dosing, with low threshold for increasing frequency of injection even to 2-weekly if required, as well as close monitoring of patients to establish individual response. There may be an increased role for slow-release steroid implants in vitrectomized eyes with DME or RVO. Longer acting substances currently under development such as brolucizumab or abicipar pegol, may become the treatment of choice in the future.

The fidelity of HPV16 E1/E2-mediated DNA replication.

Human papillomaviruses (HPV) are causative agents in a variety of human diseases; for example over 99% of cervical carcinomas contain HPV DNA sequences. Often in cervical carcinoma the HPV genome is integrated into the host genome resulting in unregulated expression of the viral transforming proteins E6 and E7. Therefore viral integration is a step toward HPV-induced carcinogenesis. Integration of the HPV genome could occur following double-strand DNA breaks that could arise during viral DNA replication. We investigated the fidelity of HPV 16 E1- and E2-mediated DNA replication of non-damaged and UVC-damaged templates in a variety of cell lines with different genetic backgrounds; C33a (derived from an HPV-negative cervical carcinoma), XP30RO (deficient in the by-pass polymerase eta (poleta)), XP30eta (expressing a restored wild-type poleta), XP12RO (nucleotide excision repair defective), and MRC5 (derived from a 14-week-old human fetus). The results demonstrate that the fidelity of E1- and E2-mediated DNA replication is reflective of the genetic background in which the assays are carried out. For example, restoring poleta to the XP30 cell line results in a 3-fold drop in the number of mutants obtained following replication of a UVC-damaged template. A relatively high percentage of the mutant-replicated molecules arise as a result of genetic rearrangement. This is the first time such studies have been carried out with an HPV replication system, and the results are discussed in the context of the HPV life cycle and what is known about HPV genomes in human cancers.