Leonardo Lando, Hatem Krema
An 85-year-old healthy White woman was assessed for extensive primary acquired melanosis involving the left bulbar conjunctiva (Fig A, B). She had no history of autoimmune disease or previous cutaneous melanoma. Her right eye showed no abnormalities. As the pigmentation had been present for at least 50 years, we opted to closely observe the patient, without any treatment. During the next 5 years, the area of pigmentation progressively decreased in area and degree of pigmentation (Fig C, D). No signs of disease relapse, skin changes, or malignancy occurred over the following 2 years. The ocular fundus remained unchanged throughout this time. Spontaneous resolution of melanosis is a rare event, sometimes triggered by infection or autoimmunity, none of which had knowingly occurred in this patient (Magnified version of Fig A-D is available online at www.aaojournal.org).
John Vekinis, Ana M Susana Morley
Background/Aims To describe the results of all ocular surface biopsies performed on patients with xeroderma pigmentosum (XP) under the care of the UK Nationally Commissioned XP Service as well as the treatment of any subsequent ocular surface conditions diagnosed.
Methods Retrospective analysis of medical records. All patients with XP seen by the service from 2010 to 2019 were included and those with ocular surface biopsies were identified. Data was collected on demographics, complementation subgroup (A–G and V), biopsy details, histopathological analysis and subsequent management.
Results Of 108 patients seen in our service, 17 underwent at least one ocular surface biopsy. 45 biopsy samples were available from 13 patients of which 65% were performed on patients from complementation subgroup C (XP-C). Biopsies were categorised as either non-mapping (clinically abnormal ocular surface tissue) or mapping (multiple sites including clinically normal tissue). 67 percent of non-mapping biopsies had a mass as their indication and 46% showed ocular surface squamous neoplasia. General non-dysplastic damage was seen in 67% of non-mapping biopsies and melanocytic changes were seen in 25% of non-mapping and 81% of mapping biopsies. 47 percent of biopsy outcomes required no additional treatment but, of those that did, 50% received mitomycin C.
Conclusions This is the largest reported series of ocular surface biopsies in patients with XP. It identifies a background of ocular surface melanocytic, degenerative and inflammatory changes, with patients with XP-C showing the most severe effects. We highlight challenges faced in interpreting their histopathology and in planning subsequent treatments.
Alexander M. Tseng, Enoch T. Peng, Shruthi H Bindiganavile, Subahari Raviskanthan, Nita Bhat, Peter W. Mortensen, Kirk E. Heyne, Andrew G. Lee
Papillary carcinoma of the thyroid gland (PCTG) constitutes 80%–85% of thyroid cancers globally. Despite early lymphatic invasion, PCTG has a relatively indolent course and rarely metastasizes outside of the neck.
Metastasis to the brain from PCTG is even more uncommon and usually occurs in the context of widely disseminated disease. While the mainstay of treatment for intracranial metastasis from PCTG includes surgical excision and radiotherapy, recent advances into our understanding of the molecular pathways governing PCTG have facilitated development of novel targeted chemotherapeutics. We present a case of superior oblique myositis that was presumed secondary to treatment of widely metastatic PCTG with dabrafenib and trametinib therapy. To our knowledge this is the first such case in the English language ophthalmic literature.
Cyril Archambault, Guy Allaire, Sonia Callejo, Georges M. Durr
A 68-year-old female was referred to the emergency ophthalmology clinic with a pigmented iris lesion and an intraocular pressure (IOP) of 38 in her left eye. Initial clinical assessment revealed the presence of a localized, flat, plaque-like peripheral and midperipheral iris lesion in one quadrant. Pigmented seeding on the rest of the iris surface and associated mild corectopia were observed. There were no notable episcleral sentinel vessels, and there was no iris neovascularization. On gonioscopy, heavy pigment invaded 8 clock hours of the angle (Fig. 1). The ciliary body was normal. Fundus examination, visual field testing, and optical coherence tomography all showed severe glaucomatous damage in the left eye (with normal testing in the right eye). The patient was initially managed medically using 4 topical glaucoma medications and systemic acetazolamide.
Charlotte A. Espensen, Jens F. Kiilgaard, Kristian Klemp, Anita Gothelf, Ane L. Appelt, Lotte S. Fog
Current standard treatment procedures for Ruthenium-106 (Ru-106) brachytherapy for choroidal melanomas do not use 3D image-guided treatment planning. We evaluated the potential impact of introducing 3D treatment planning and quantified the theoretical clinical benefits in terms of tumour control probability (TCP) and normal tissue complication probability (NTCP).
Materials and methods
Treatment plans for thirty-two patients were optimized using 3D image-guided treatment planning and compared to the original 2D clinical plans. Optimization of plans was done in an image-based treatment planning system by optimizing the plaque position and treatment time such that the entire tumour received the prescribed dose of 100 Gy. TCP and NTCP for 2D clinical plans and optimized 3D image-guided plans were estimated from published outcome prediction models and compared within patients using Wilcoxon signed-rank test.
The median minimum tumour dose (D99%) for 2D clinical plans was 93 Gy (range: 23–158 Gy), corresponding to 5-year TCP of 75% (IQR 61–86%), while median tumour D99% for optimized 3D image-guided plans was 115 Gy (range 103–141 Gy), corresponding to TCP of 82% (IQR 80–84%). This was a statistically significant increase in estimated TCP (median increase in TCP 8% (IQR: −5–23, p = 0.006). While the dose to normal tissue increased somewhat, there was no significant change in NTCP.
3D treatment planning theoretically allows for improved tumour dose delivery for Ru-106 brachytherapy of choroidal melanomas, resulting in a significant increase in expected tumour control compared to traditional approaches using 2D calculations. The deliverability of optimized plans, and potential increased risk of late complications, will have to be confirmed in future clinical studies.
Ingvild Ramberg, Michael Møller-Hansen, Peter Bjerre Toft, Mikkel Funding, Steffen Heegaard
We aimed to study the prevalence of human papillomavirus (HPV) in conjunctival intraepithelial neoplasia and carcinoma. Furthermore, we aimed to explore whether geographical differences or different detection modalities are associated with the conflicting information regarding HPV and the development of the disease.
We searched the MEDLINE, EMBASE and Scopus databases for studies reporting on HPV and conjunctival intraepithelial neoplasia or carcinoma. The pooled prevalence proportions, odds ratio (OR) and corresponding 95% confidence intervals were calculated assuming a random-effects model. Subgroup analyses and meta-regression explored possible sources of heterogeneity.
A total of 39 studies were included in the systematic review. The pooled prevalence of HPV in conjunctival intraepithelial neoplasia and carcinoma was 26%, with HPV16, 18, and 33 being the most frequently reported genotypes. Human papillomavirus (HPV) infection was associated with an increased risk of conjunctival intraepithelial neoplasia and carcinoma (OR 8.4, 95% confidence interval (CI) 3.7–19.1); lower in studies from African countries (OR 1.7, 95% CI 0.9–3.5) than other countries (OR 16.1, 95% CI 5.8–44.3), p = 0.013.
Human papillomavirus infection increases the odds of conjunctival intraepithelial neoplasia and carcinoma by 8.4 compared to healthy conjunctival mucosa or other ocular surface diseases. There seem to be geographical differences regarding HPV in conjunctival intraepithelial neoplasia and carcinoma. HPV16 was the most prevalent genotype, followed by HPV18 and HPV33, meaning that most of the HPV-related conjunctival intraepithelial neoplasia and carcinoma may be prevented by the HPV vaccines that are currently available.
Renato Jose Yupari, James Bena, Allan Wilkinson, John Suh, Arun Singh
Aim To assess the outcomes of small choroidal melanoma following iodine-125 episcleral brachytherapy (apical height dose of 85 Gy).
Methods Patients with small choroidal melanoma that underwent iodine-125 episcleral brachytherapy between January 2004 and December 2017 were reviewed. Inclusion criterion for this study was the COMS small tumour size (tumour apical height of 1.0–2.5 mm and largest basal diameter (LBD) <16.0 mm). Patients that received any form of prior therapy or adjuvant transpupillary thermotherapy were excluded. Outcome measures were visual acuity (VA), recurrence, ocular survival and metastasis at 3 years. Kaplan-Meier estimation was calculated for VA, recurrence, ocular survival and survival outcome (overall and metastasis-free survival rate) at 3 years.
Results 161 cases of choroidal melanoma were included in this study, with the mean (SD) age of 59.6 (14.1) years, and 93 (58%) were males. The mean (SD) apical height for the tumours were 2.1 (0.4) mm and mean (SD) LBD was 8.3 (2.2) mm. The mean (SD, median) follow-up was 40.7 months (37.1, 25 months). The VA was 20/50 or better in 69%. Only one recurrence event (1%) and one enucleation event (1%) were observed. Overall survival was 97%, and no metastatic events were observed at 3 years.
Conclusion Small choroidal melanomas treated with iodine-125 episcleral brachytherapy have excellent outcomes. The majority (69%) of patients retained VA of 20/50 or better with very high local control and ocular survival rate (99.3%) with the absence of metastasis (100%).
Vijitha S Vempuluru, Saumya Jakati, Swathi Kaliki
To discuss the clinical presentation, management, and outcome of delayed metastasis in retinoblastoma (RB).
Retrospective case series of three patients.
Mean age at diagnosis of RB was 29 months (median, 28 months; range, 11–48 months). All were males with non-familial bilateral intraocular RB. Primary treatment for RB included intravenous chemotherapy in all three cases. Secondary treatment included transpupillary thermotherapy/cryotherapy (n = 6 eyes), periocular chemotherapy (n = 2 eyes), intravitreal chemotherapy (n = 1 eye), intra-arterial chemotherapy (n = 1 eye), external beam radiotherapy (EBRT; n = 2 eyes), and enucleation (n = 2 eyes). Primary tumor regression was achieved in all cases and remained status quo at the time of diagnosis of distant metastasis. Two patients developed bone metastasis (ulna; tibia) and one developed soft tissue metastasis (temporal fossa) over a mean follow-up period of 6 years (median, 7 years; range, 5–8 years) from diagnosis of RB. Mean age of detection of metastatic disease was 8 years (median, 8 years; range, 7–9 years). All the lesions were solitary and the diagnosis of metastatic retinoblastoma was confirmed by tissue biopsy. Metastatic disease was treated with surgical excision (n = 1), chemotherapy (n = 2), and EBRT (n = 2). All patients are alive, with two patients free of disease over a mean follow-up period of 23 months (median, 23 months; range, 12–33 months); and 1 in remission 7 months after completion of EBRT.
Long-term follow-up of RB cases is mandatory. In spite of intraocular tumor regression, metastasis can still occur many years after treatment of RB.
Sari Yordi, Hansell Soto, Randy C. Bowen, Arun D. Singh
To determine the response rate of choroidal melanoma following primary photodynamic therapy, we conducted a meta-analysis of published studies. A total of 7 studies reporting photodynamic therapy as primary treatment of choroidal melanoma in 162 patients with a mean tumor height of 2.8 mm (1.4 to 4.2) were identified. Forty-six percent of tumors were amelanotic, 48% were fully pigmented, and 6% had partial pigmentation. The photodynamic therapy parameters in all studies included 10-minute intravenous infusion of verteporfin (6 mg/m2), but varied in number of sessions (1 to 3), fluence (1× to 19×), and number of spots (single or multiple). The response was defined as tumor regression (partial or total) or lack of growth after initial treatment. The response to photodynamic therapy was predominantly observed as regression (126 [78%]). Overall response rate was 80% (mean) with a wide range among studies (58%–100%) over a period of 50 months (mean) with variable follow-up (range, 1–156 months). None of the studies reported progression- or recurrence-free survival; however, the recurrence rate was not related to the follow-up duration. Favorable prognostic factors were smaller size and lack of pigmentation. The overall response rate of 80% suggests that photodynamic therapy may be an effective primary treatment for small choroidal melanoma, especially in cases without pigmentation. Artifacts in study design (inclusion criteria and outcome measure) may have contributed to the variable observed response rate. Further studies with uniform inclusion criteria, standardized treatment parameters, well-defined outcome measures, and long follow-up are needed.