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Purpose: To evaluate the clinicopathological characteristics and the effectiveness of post-operative high-dose-rate (HDR) interventional radiotherapy (IRT - brachytherapy) in managing advanced ocular surface squamous neoplasia (OSSN) and eyelid tumors., Methods: Nineteen patients with advanced malignancies affecting the ocular surface (stage ≥ T2) and eyelids (staging ≥ T3) were enrolled. Post-operative HDR-IRT treatment followed surgery after multidisciplinary discussion. In our series a total dose of 49 Gy was administered in 14 fractions of 3.5 Gy each, 2 doses per day. Local disease control is the study's main outcome. Death rate, total survival, disease-free survival, and toxicity are secondary outcomes., Results: Local recurrence was observed in 4 cases, 2 were conjunctival melanomas and 2 were conjunctival squamous cell carcinoma. The median OS was 56.3 months. The 12, 24 and 36 months survival rate was respectively 100.00% (IQR: 100.00% - 100.00%), 100.00% (IQR: 100.00% - 100.00%), 100.00% (IQR: 100.00% - 100.00%) respectively . The median DFS was 56.3 months. The 12, 24 and 36 months disease survival rate was respectively 85.71% (IQR: 69.21% - 100.00%), 68.57% (IQR: 42.11% - 100.00%), 68.57% (IQR: 42.11% - 100.00%) respectively. In eyelid tumors, madarosis and eyelid abnormalities are the main side effects, while in OSSNs, dry eye symptoms are frequently reported., Conclusion: Postoperative HDR-IRT has been effective in advanced eyelid cancers control. More challenging appears instead an effective treatment of advanced OSSNs, particularly conjunctival melanomas. Multicenter studies are needed to get a larger patient sample and to evaluate different radiotherapy dosages by different histologic and T types of tumors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

The extended depth-of-focus AcrySof IQ Vivity intraocular lens technology offers promising features for presbyopia management, evaluated in this research in a 6 months real-world setting. Prospective interventional mono-centric study including 40 patients who underwent elective bilateral phacoemulsification. We performed one pre-operative visit (V0) and one evaluation six months post-operatively (V1), evaluating uncorrected and corrected visual acuity for near (UNVA/CNVA), intermediate (UIVA/CIVA) and far (UDVA/UCVA), slit-lamp evaluation, tomography with static pupillometry, endothelial cell count and contrast sensitivity chart. In order to assess post-operative Quality of Life, we administered the patients McAlinden's Quality of Vision test and Morlock's Patient-Reported Spectacle Independence Questionnaire. We divided eyes in with Toric-IOL and with non-Toric IOL. A total of 36 eyes received non-tonic IOL implantation, whereas 44 eyes received toric IOL implantation. There were no statistically significant disparities observed in visual outcome measures and contrast sensitivity between the toric group and the non-toric group. Furthermore, we assessed the predictive preoperative refractive astigmatism (PPRA) and residual refractive astigmatism (RRA) in both cohorts, and no statistical significance was found between the two cohorts (p = 0.08). Twenty-one (53%) patients reported total independence from their glasses at all distances. The mean difference between the predicted and measured refractive error, as calculated by spherical equivalent, was 0.09 D. AcrySof IQ Vivity is a well-tolerated and effective IOL with optimal refractive target for both distant and intermediate vision, needing slight spherical addition for the best near vision. Great questionnaire-based satisfaction was reported by the patients., (© 2024. The Author(s).)

Background: We report a case of personalized exclusive brachytherapy treatment for the management of a highly recurrent squamous cell conjunctival carcinoma with corneal invasion., Case Description: This is a case of a Caucasian 81-years-old man who presented 10 years ago to our clinic with a pink-white para-limbal mass with dilated feeder arteries and mild leukoplakia. Excisional biopsy confirmed the presence of conjunctival intraepithelial neoplasia (CIN). Successively, he underwent two 4-weeks cycles of Mytomicin C topical therapy and a second excisional surgery, due to several recurrences of the lesion. At the last relapse, the pink-white peri-limbic mass which invaded the corneal limbus, determining corneal opacification from 5- to 7-clock hours, was confirmed by anterior segment optical coherence tomography (AS-OCT). Due to resistance to MMC therapy and chronic epitheliopathy, an AS-OCT guided exclusive radiotherapy plan was set: a Rhutenium-106 CCD plaque was applied directly over the afflicted corneal surface, the corneal limbus and the neighboring sclera for 24 hours. The remission of both conjunctival and corneal malignancy was complete 2 months after surgery and no signs of recurrence were highlighted at AS-OCT analysis at the 2-year follow up., Conclusion: Brachytherapy treatment showed optimal management of both corneal and conjunctival involvement, with a free-of-disease follow-up of 24-months. This result suggests that, in specific conditions, Ru-106 brachytherapy could be an effective option of treatment even if not associated with surgical excision., Competing Interests: Disclosures The authors declare no conflict of interests. This research did not receive any specific grant from funding agencies in public, commercial or not-for-profit sectors., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The main purpose of treatment of advanced ocular surface and periocular malignant tumors is to eradicate the tumor while trying to preserve visual function and aesthetics. Our purpose is to describe the outcome of a retrospective case series of 10 patients with advanced ocular surface and periocular tumors treated surgically in first instance and then with postoperative interventional radiotherapy (IRT/Brachiterapy)., Materials and Methods: We describe the clinicopathological features, treatments and outcome, in a retrospective case series of 10 patients with advanced tumors involving ocular surface (staging ≥ T2) and eyelids (staging ≥ T3), with involvement of periocular and/or orbit tissues. Patients were first surgically treated, most of them with incomplete excision, and then underwent a post-operative interventional radiotherapy (IRT/Brachytherapy) as an alternative to more invasive and disfiguring surgical retreatment. Tumor location, risk factors, staging, histological features, and follow-up timing were analyzed., Results: Three patients had advanced eyelid basal cell carcinomas, 2 patients were diagnosed with eyelid and conjunctival squamous cell carcinomas, 3 as sebaceous carcinomas, and 2 as primary conjunctival melanomas. The mean follow-up time from IRT to last clinical follow-up was 58.6 weeks, range 28.4-168 (median 43.65, IQR 28.9-72.9). Two patients - one with ocular surface SCC, the other with conjunctival melanoma - had a local recurrence 23.4 and 40,9 weeks after IRT, respectively. An overview of the current knowledge on adjuvant or post-operative IRT is also provided., Conclusions: IRT can be considered an effective therapeutic option to avoid more invasive surgical retreatment in advanced tumors involving eyelids and ocular surface., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The migration of silicone oil into the suprachoroidal region is a rare complication of vitrectomy. A 70-year-old man was admitted to our ocular oncology unit with a choroidal elevation in the nasal area, as well as signs of pars plana vitrectomy surgery performed about 5 years ago for retinal detachment. The patient underwent ocular ultrasound, visual field test, fluorangiography, and magnetic resonance imaging, which led to the diagnosis of silicone oil migration in the suprachoroidal space. Silicone oil may move into the suprachoroidal area, mimicking choroidal neoformation. It is important to have a comprehensive diagnosis and then set up the appropriate treatment. [ Ophthalmic Surg Lasers Imaging Retina 2024;55:104-108.] .

Background: Periocular malignancies may be clinically different from the examples arising at other sites, with possible delayed diagnosis and greater challenges for treatment and repair. Line-field confocal optical coherence tomography (LC-OCT) is a recently developed technique characterized by an unprecedented capacity to acquire high-definition images in vertical and horizontal modes. In this study, we aimed to investigate the LC-OCT morphological features of a series of eyelid skin lesions, correlating them to histopathological findings., Methods: Patients with biopsy-proven equivocal skin lesion in the eyelid area, previously investigated by means of LC-OCT, were included in the study. Percentage overall agreement was estimated for LC-OCT and histopathological diagnosis for study cases., Results: A total of 51 patients (28 women, 23 men; mean age 66.4 years old), for a total of 51 skin lesions, were assessed. The histopathological diagnosis consisted of 30 malignant and 21 benign tumors. Different entities were characterized by peculiar findings in LC-OCT, alike to histopathological features, allowing for an accurate "in vivo" classification in almost all cases, with a diagnostic concordance with histopathology of 92.1% (47/51)., Conclusions: By integrating this new imaging technique into the assessment of suspicious tumors in this area, diagnostic accuracy may increase, improving strategies adopted in multidisciplinary meetings and patient-centered care.

Uveal melanoma represents the most common intraocular neoplasia among adults. Brachytherapy (interventional radiotherapy; IRT) has a great advantage, when compared with enucleation, both in terms of organ and function sparing. The Collaborative Ocular Melanoma Study introduced into clinical practice a standardised procedure that allowed the equivalence of IRT with enucleation in terms of overall survival to be demonstrated. IRT is carried out by placing a plaque in direct contact with the sclera under the uveal melanoma. Several radioactive sources may be used, including 106-ruthenium, 125-iodine, 103-palladium and 90-strontium. It is a multidisciplinary procedure requiring the collaboration of interventional radiation oncologists and ophthalmologists in the operating theatre and medical physicists for an accurate treatment time calculation. It also relies on ultrasound imaging to identify the lesion and verifiy the correct plaque placement. An emerging tool of paramount importance could be the use of artificial intelligence and predictive models to identify those patients at higher risk of developing late side-effects and therefore who may deserve preventive and supportive therapies., (Copyright © 2023 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Purpose: Since there is a lack of clear information regarding the benefit to combine supportive therapies (such as artificial tears) to mitomycin C (MMC) in the treatment of ocular surface neoplasia, the primary purpose of the study was to evaluate hyaluronic acid eye drops and hyaluronic acid-conjugated lactobionic acid (LACTOyal FREE) eye drops as supportive therapy., Methods: Retrospective evaluation of patients with ocular surface squamous neoplasia or conjunctival melanocytic tumor treated with MMC, who had used also artificial tears as supportive treatment. A 6-month follow-up with evaluation of subjective and objective tests for ocular surface integrity was conducted., Results: A total of 35 patients were analyzed, most of them with squamous disease (71.4%). The break-up time (BUT), Ocular Surface Disease Index (OSDI) and Schirmer test values showed a significant difference at any time point with overall population. No statistical difference was found among subgroups (Lactoyal vs No Lactoyal)., Conclusion: The use of an ancillary therapy based on hyaluronic acid allows to improve both subjective and objective ocular parameters, reducing MMC induced adverse effects. Meantime, hyaluronic acid-conjugated lactobionic acid eye drops highlighted the same advantages with a more positive trend in OSDI results., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Uveal melanoma is the most common ocular tumor with frequent metastatic spread to the liver. Immune checkpoint inhibitors have demonstrated poor results in this disease. The addition of hepatic radiotherapy to anti-PD-1 could enhance the sensitivity to immunotherapy. In this study, patients treated with pembrolizumab and who have undergone hepatic radiotherapy have been retrospectively evaluated. Twenty-two patients have been considered. Six patients (27.3%) achieved a partial response and 3 (13.6%) a stable disease. Disease control rate was 40.9%. Thirteen patients (59.1%) had progression as best response. The median PFS was 4.8 months and 6 months PFS rate 45.4%. The median OS was 21.2 months, while 1 year OS rate was 72.7%. Longer survival was observed in patients who achieved a partial response on irradiated metastases (HR 0.23, 95% CI 0.06-0.83) or progressed after 6 months (HR 0.12-95% CI 0.03-0.44). No radiotherapy-related or grade 3-4 adverse events were reported. This study demonstrates that the addition of hepatic radiotherapy to anti-PD-1 treatment can be a valid option for the treatment of metastatic uveal melanoma, particularly for HLA A 02:01 negative patients. Prospective studies should be conducted to confirm these data.

Purpose: The complexity of multimodal approaches in cancer management has lately led to the establishment of multidisciplinary tumor boards (MDTBs) to define targeted, patient-centered treatment strategies. However, few data are available regarding the application of this approach in Ocular Oncology. Hereby, the Authors analyze the implementation and outcomes of a trained MDTB in a tertiary ocular oncology referral center., Methods: A retrospective descriptive analysis of MDTB meetings discussing patients with ocular and periocular cancers, over a 12-months period, was carried out. Data were grouped by main site involved, topics discussed and final clinical decisions therefore taken. Meetings were held by a constant 'Core team' or - when required - by a broader 'Extended team'., Results: During the observational period 86 cases were discussed. In 27 patients ocular surface tissues were involved (31%), in 25 patients orbital tissues (29%), in 22 patients eyelids (26%), and in 12 patients intraocular tissues (14%). In 13 cases (15%) naïve or referred new patients, in 34 cases (40%) imaging or histopathologic reports and in 39 cases (45%) treatment plans were discussed. Regarding final decisions, a treatment plan was scheduled in 47 cases (55%) and a diagnostic ascertainment was required in 27 patients (31%); locally advanced and/or systemic diseases were referred or teamed up with other specialists in 12 cases (14%)., Conclusions: Ocular Oncology multidisciplinary team, by sharing expertise of different specialists, ensures a comprehensive evaluation of patients improving the accuracy of diagnosis and staging upon which planning a proper treatment. Further studies are needed to assess if this approach may also improve the outcomes and prognosis of patients., (© 2022. The Author(s).)

Purpose: To evaluate the effect of photodynamic therapy (PDT) as adjuvant treatment, after brachytherapy, in posterior amelanotic choroidal melanomas., Methods: Six patients with posterior amelanotic choroidal melanoma underwent brachytherapy treatment. Tumour response was assessed by fundus examination, fundus photography and A-B scan ultrasonography. The residual tumours were treated with adjuvant PDT performed with infusion of verteporfin intravenously at 6 mg/m 2 body surface area. Five minutes after infusion, a 689 nm laser was applied with a light dose of 100 J/cm 2 over an interval of 166 s., Results: At a median follow-up after brachytherapy of 17.5 months (IQR 16.2-22.5, range 5-42 months), tumours showed a partial reduction of tumour thickness (22.5% as compared to baseline value) and persistent low internal reflectivity at A-B scan ultrasonography. Supplementary photodynamic treatment resulted in complete resolution of the lesion with marked decrease of elevation . Mean decrease in thickness after PDT was 49.9% with respect to previous brachytherapy treatment 22.5% (p = 0.007). The results was achieved within a median period of 4 months (range 2-4 months) after PDT, and there has been no recurrence after a median follow-up of 84.7 months ± 18.7 (range 59 to 107 months)., Conclusion: Combined treatment of brachytherapy and adjuvant PDT in amelanotic uveal melanoma seems to be favourable with regard to complete and rapid tumour regression.

Primary malignant epithelial tumours arising from accessory lacrimal glands (ALGs) are extremely rare, with only few cases reported in literature. They generally appear as gradually increasing masses of the upper or the lower eyelid. Only one case of primary adenocarcinoma or adenocarcinoma not otherwise specified (ACNOS) from ALGs has been reported in literature. Herein, we describe a case of ACNOS arising from ALGs with an atypical clinical presentation and review prior cases of ALGs epithelial malignancies reported in the literature. A 78-year-old man referred to our Ocular Oncology Unit for adjuvant therapy after the excision of a conjunctival tumour of the left eye with a histological diagnosis of squamous cell carcinoma. He underwent topical chemotherapy with MMC and during follow up he presented a multinodular iris mass in his left eye. The MRI of the orbit showed an ocular mass infiltrating orbital soft tissues of the inferior palpebral region with an involvement of the corresponding zygomatic cutis. We performed orbital exenteration and histological studies revealed an epithelial neoplasm with a solido-glandular growth pattern with lumens containing an eosinophilic material positive for PAS and PAS-D. The immunohistochemical findings confirmed the diagnosis of adenocarcinoma NOS from ALGs. Although ALGs epithelial malignancies are extremely uncommon, they should be considered in the differential diagnosis of ocular tumours. A vigilant approach towards these entities is required, since they can be clinically insidious and locally aggressive.

Purpose: To report a case of macular choroidal osteoma treated with photodynamic therapy., Observations: A 34-years old woman with decreased visual acuity in her left eye came to our observation for assessment of an amelanotic choroidal tumor in the left eye. On the basis of ophthalmoscopic and echographic features the tumor was diagnosed as choroidal osteoma. Imaging examination revealed subretinal fluid involving the foveal area associated with alterations of outer neuroepithelial layers and photoreceptors without evidence of choroidal neovascularization. Foveal sparing standard fluence rate photodynamic therapy was performed. After treatment, subretinal fluid reabsorption and visual acuity recovery was noted with progressive restoration of foveal architecture. Due to the relapse of fluid and visual impairment, 1 year after treatment, a second PDT session was made using the same parameters and protocol of treatment. Despite a complete subretinal fluid reabsorption and visual acuity recovery the second treatment was complicated by the development of subretinal fibrosis., Conclusions: PDT is effective to induce subretinal fluid reabsorption and visual recovery in choroidal osteoma located in the macular area. However, the risk of possible complications related to the treatment have to be considered.

Purpose: Orbital pseudotumor (or pseudotumor orbitae) is a benign entity, also known as idiopathic orbital inflammatory syndrome (IOIS), which encompasses a wide range of non-tumoral, space occupying lesions of the orbit. In selected cases of refractory disease or presence of side effects or even comorbidities that limit systemic therapies, radiotherapy could play a role in the management because it has been demonstrated that irradiation is effective in suppressing the inflammatory process., Methods: A systematic review of the literature about the main scientific databases was launched and the time interval included all published articles present in the databases from their inception until September 2020., Results: We were able to identify 19 studies eligible for inclusion in this review from 1978 to 2018. Overall the data of 241 patients were collected and are presented in this systematic review. The response rate varied between 74% and 100% with a median recurrence rate of 10%. The median total dose was 20 Gy whereas the mean total dose was 21 Gy with a range from 4 to 36 Gy. Regarding the fractionation, 2 Gy/fraction daily was the most widely used., Conclusions: Radiotherapy seemed to achieve good response rates however, in most of the studies, inclusion criteria and outcome parameters are not uniform and therefore the results are difficult to compare. Often important parameters such as chronic pain and permanent functional deficits are not assessed in the outcome. Therefore, prospective studies, with good cohort characteristics and a clear definition of the outcome, are required.

(1) Background: Periorificial face cancer (PFC), defined as both squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) arising around the eyelids, the nose vestibule and the lips, has very high incidence rates worldwide. The aim of our retrospective analysis, focusing on local control (LC) and patients' degree of satisfaction with the cosmetic outcome, is to present the results of a single institutional series of patients affected by PFC and treated by interventional radiotherapy (brachytherapy-IRT). (2) Methods: We retrospectively evaluated patients affected by PFC who were treated at our Interventional Oncology Center (IOC) with interstitial IRT from 2012 to 2021 with doses and volumes specific for each subsite considered. (3) Results: We report the results of 40 patients affected by PFC and treated by HDR interstitial IRT. The median follow-up was 24 months. The actuarial 3-year LC was 94%. Regarding patients' satisfaction, we found that 93% of patients were satisfied and only 7% of patients were not completely satisfied with the final cosmetic result. (4) Conclusions: Interstitial HDR IRT could be an effective therapeutic option providing adequate disease control and preventing potentially disfiguring surgical approaches. More numerous and standardized studies are warranted to confirm the available evidence.

Metastatic uveal melanoma (UM) is a poor prognosis malignancy. Immunotherapy is commonly employed, despite the low activity, considering the lack of other effective systemic treatments. In this study, the prognostic and predictive role of soluble immune checkpoints and inflammatory cytokines/chemokines in 22 metastatic UM patients was evaluated. Baseline levels of these molecules were assessed, as well as their changes during anti-PD-1 therapy. The correlation between soluble immune checkpoints/cytokines/chemokines and survival was analyzed. A comparison between circulating immune profile of metastatic cutaneous melanoma (CM), for which immunotherapy is a mainstay of treatment, and UM during anti-PD-1 therapy was also performed. Three immune molecules resulted significantly higher in metastatic UM patients with survival <6 months versus patients with survival ≥6 months: IL-8, HVEM and IDO activity. Considering these three molecules, we obtained a baseline score able to predict patients' survival. The same three molecules, together with soluble(s) CD137, sGITR and sCD27, resulted significantly lower in patients with survival >30 months. We also observed an increase of sCD137, sCD28, sPD-1, sPD-L2 sLAG3, sCD80 and sTim3 during anti-PD-1 treatment, as well as IDO activity, IP-10 and CCL2. Several of these molecules were significantly higher in UM compared to CM patients during anti-PD-1 therapy. The analysis of circulating immune molecules allows to identify patients with poor prognosis despite immunotherapy and patients with long survival treated with an anti-PD-1 agent. The different serum concentration of these molecules during anti-PD-1 therapy between UM and CM reflects the different efficacy of immune checkpoint inhibitors.

Melanoma is an extremely aggressive tumor and is considered to be an extremely immunogenic tumor because compared to other cancers it usually presents a well-expressed lymphoid infiltration. The aim of this paper is to perform a multidisciplinary comprehensive review of the evidence available about the combination of radiotherapy and immunotherapy for melanoma. Radiation, in fact, can increase tumor antigens visibility and promote priming of T cells but can also exert immunosuppressive action on tumor microenvironment. Combining radiotherapy with immunotherapy provides an opportunity to increase immunostimulatory potential of radiation. We therefore provide the latest clinical evidence about radiobiological rationale, radiotherapy techniques, timing, and role both in advanced and systemic disease (with a special focus on ocular melanoma and brain, liver, and bone metastases) with a particular attention also in geriatric patients. The combination of immunotherapy and radiotherapy seems to be a safe therapeutic option, supported by a clear biological rationale, even though the available data confirm that radiotherapy is employed more for metastatic than for non-metastatic disease. Such a combination shows promising results in terms of survival outcomes; however, further studies, hopefully prospective, are needed to confirm such evidence.

The goal of radiotherapy in the treatment of eyelid and ocular surface tumors is to eradicate tumor burden in a manner that maintains visual function and preserve surrounding sensitive ocular tissue. Interventional radiotherapy (IRT-brachytherapy) is a radiotherapy technique associated with a highly focal dose distribution, with the advantage of boosting limited size target volumes to very high dose while sparing normal tissue. The reduction in the ocular and adnexal complications that result from this form of therapy, has led in recent years, to an increase in the use of IRT for the treatment of eyelid and ocular surface tumors. For eyelid malignancies, IRT is used as an independent treatment in small eyelids tumors, in postoperative treatment of high-risk patients and as well as salvage therapy in local recurrences. In the treatment of conjunctival malignancies, due to the high risk of local recurrence, the use of adjuvant therapies as IRT has shown to improve outcomes. In this review, we focus on eyelid and ocular surface IRT techniques and provide an overview of indication, outcomes and toxicity of IRT for the treatment of naïve and recurrent eyelid and conjunctival tumors., Competing Interests: The authors declare that no conflicts of interest exist., (© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)

Uveal melanoma (UM) is the most common intra-ocular tumor in Caucasian adults and may derive from melanocytes. Historically, the first therapeutic approach to treat UM has been surgical removal of the eye, with obvious consequences in terms of function, cosmesis, and psychological impact on patients. Collaborative Ocular Melanoma Study (COMS) introduced the first uniform approach to perform interventional radiotherapy (IRT - brachytherapy) procedure in a standardized way that allowed to demonstrate equivalence of IRT with enucleation in terms of overall survival. Since this milestone, several international guidelines have been issued with regard to several technical aspects of this procedure, which has become the mainstream therapy worldwide. However, nowadays, there is still a lack of consensus about the criteria to definitively assess UM response after IRT. We present a collection of paradigmatic cases treated in our institution, and then discuss in detail the latest available evidence on the topic., Competing Interests: The authors report no conflict of interest., (Copyright © 2022 Termedia.)

Purpose: To analyze the clinical characteristics and long-term follow-up of patients with advanced ocular surface squamous cell carcinoma (OSSC) involving periocular tissues and/or orbit. Primary outcomes were overall survival (OS), disease-free survival (DFS), and overall recurrence rate (RR). Secondary outcomes were a correlation between primary outcomes and tumor location, American Joint Committee on Cancer Classification (AJCC) staging system, histological results, surgical margins, and type of treatment., Study Design: a retrospective case series., Methods: The medical records of patients affected by OSSC involving periocular tissues and/or orbit referring, from 01/2011 to 01/2020, to our tertiary referral center were reviewed., Results: Thirty-six eyes of 36 patients were included. The mean age was 68.2 years; 18 (50%) patients were males. The mean follow-up was 40 months. The RR was 64%. The OS at 12, 24, 36, and 60 months was respectively 97.1%, 92.7%, 92.7%, and 92.7%. The DFS at 12, 24, 36, and 60 months was respectively 62.9%, 50.8%, 41.6%, and 29.7%. Multicentric disease (p = 0.0039), inferior tarsus localization (p = 0.0428), histological diagnosis of high-risk SSCs (p = 0.0264), positive surgical margins (p = 0.0434), and excisional biopsy (EB) alone (p = 0.0005) were associated with an increased risk of recurrence. A shorter OS was observed in patients who underwent EB alone (p = 0.0049)., Conclusion: OSCC involving periocular tissues and/or orbit is an aggressive disease with a high recurrence rate. Multicentric disease, positive surgical margins, inferior tarsus localization, and surgery without adjuvant therapies are strong predictors of recurrence and are the main factors affecting prognosis., (© 2021. The Author(s).)

Background/objectives: Fluorescein angiography (FA) has been a pivotal tool to study the pathophysiology of retinopathy of prematurity (ROP) in vivo. We examined the course of ROP using FA in order to assess the predictive value of angiographic features., Subjects/methods: This is an observational retrospective cohort multi-center study of eyes screened for ROP with binocular indirect ophthalmoscope and with FA. All infants undergoing screening examination for ROP who had retinal vasculature limited to Zone I and posterior Zone II vascularization underwent FA between 31 and 34 weeks postmenstrual age. RetCam fundus imaging and video digital fluorescein angiography were performed in the neonatal intensive care units. Masked grading of the FA images was retrospectively conducted by two ROP expert ophthalmologists. Ten criteria that describe retinovascular and choroidal features on FA were used to assess their predictive value for development of treatment-requiring ROP., Results: A total of 98 eyes of 56 patients were included for this study. FAs of eyes of premature infants show a wide range of features either at the junction between the vascular and avascular retina and posteriorly to that. Among the angiographic features evaluated, leakage, shunts and hyperfluorescent lesions at the junction between vascular and avascular zone were predictive of the development of treatment-requiring ROP (p < 0.05), but findings in the posterior vascularized retina were not., Conclusions: FA can add to our understanding of the evolution of vascular abnormalities in the course of ROP and can help predict which eyes will go on to treatment., (© 2020. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Introduction and Purpose: Choroidal metastases (CM) are the most common intraocular malignancies. With longer survival rates for cancer patients, CM will be increasingly encountered. We evaluated clinical and ultrasonographic (US) characteristics of CM in order to identify diagnostic biomarkers that correlate with the primary tumor site., Methods: The medical records of all patients with CM evaluated at the Ocular Oncology Unit between February 2010 and March 2020 were analyzed., Results: 82 eyes of 70 patients were included. The primary cancer site was lung in 26 patients (37%), breast in 23 (33%), kidney in 9 (13%), gastrointestinal in 5 (7%), thyroid in 5 (7%), parathyroids and prostate respectively in 2 (3%). Fifty-five patients (78%) had other systemic metastases at the time of ocular diagnosis. Ten (14%) patients had no history of primary cancer. Bilateral CM were found in 20 patients (29%); fifty-six eyes (68%) had a single CM. The epicenter of CM was predominantly macula (43 eyes, 52%). The mean thickness was 4,1 mm (range 1,8-12,3). US structure was inhomogeneous in 67 eyes (82%). Reflectivity was mainly medium (39%) and medium-low (39%). In particular, CM from lung cancer showed lower reflectivity than those from the breast (p = 0,02). CM deriving from lung cancer were typically dome-shaped, whereas CM originating from breast were characteristically plateau shaped (p = 0,02). Seventy-four (91%) eyes presented fluid on optical coherence tomography., Conclusion: We significatively found that CM from lung cancer generally appear dome-shaped with medium-low internal reflectivity, whereas those from breast cancer typically present a plateau appearance and higher internal reflectivity. Though it is hard to identify the site of the primary tumor relying exclusively on clinical and US aspects, morphology and internal reflectivity can be considered as diagnostic biomarkers. Thus, the origin of the primary tumor can be suspected by integrating a constellation of findings., Competing Interests: The authors have declared that no competing interests exist.

Immunotherapy can be used for cutaneous, mucosal, uveal and conjunctival melanoma. Nevertheless, we cannot expect the same benefit from checkpoint inhibitors for all the types of melanoma. The different biological features can explain the variable efficacy. The main results obtained with immune checkpoint inhibitors in the various types of melanoma were reviewed.

Purpose: The purpose of this study was to explore the use of fluorescein angiography (FA) images in a convolutional neural network (CNN) in the management of retinopathy of prematurity (ROP)., Methods: The dataset involved a total of 835 FA images of 149 eyes (90 patients), where each eye was associated with a binary outcome (57 "untreated" eyes and 92 "treated"; 308 "untreated" images, 527 "treated"). The resolution of the images was 1600 and 1200 px in 20% of cases, whereas the remaining 80% had a resolution of 640 and 480 px. All the images were resized to 640 and 480 px before training and no other preprocessing was applied. A CNN with four convolutional layers was trained on 90% of the images ( n = 752) randomly chosen. The accuracy of the prediction was assessed on the remaining 10% of images ( n = 83). Keras version 2.2.0 for R with Tensorflow backend version 1.11.0 was used for the analysis., Results: The validation accuracy after 100 epochs was 0.88, whereas training accuracy was 0.97. The receiver operating characteristic (ROC) presented an area under the curve (AUC) of 0.91., Conclusions: Our study showed, we believe for the first time, the applicability of artificial intelligence (CNN) technology in the ROP management driven by FA. Further studies are needed to exploit different fields of applications of this technology., Translational Relevance: This algorithm is the basis for a system that could be applied to both ROP as well as experimental oxygen induced retinopathy., Competing Interests: Disclosure: D. Lepore, None; M.H. Ji, None; M.M. Pagliara, None; J. Lenkowicz, None; N.D. Capocchiano, None; L. Tagliaferri, None; L. Boldrini, None; V. Valentini, None; A. Damiani, None, (Copyright 2020 The Authors.)

Aim: The aim of this study was to detect clinical factors predictive of loss of visual acuity after treatment in order to develop a predictive model to help identify patients at risk of visual loss., Patients and Methods: This was a retrospective review of patients who underwent interventional radiotherapy (brachytherapy) with 106 Ru plaque for primary uveal melanoma. A predictive nomogram for visual acuity loss at 3 years from treatment was developed., Results: A total of 152 patients were selected for the study. The actuarial probability of conservation of 20/40 vision or better was 0.74 at 1 year, 0.59 at 3 years, and 0.54 at 5 years after treatment. Factors positively correlated with loss of visual acuity included: age at start of treatment (p=0.004) and longitudinal basal diameter (p=0.057), while distance of the posterior margin of the tumor from the foveola was inversely correlated (p=0.0007)., Conclusion: We identified risk factors affecting visual function and developed a predictive model and decision support tool (AVATAR nomogram)., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Conjunctival melanoma (CjM) is a rare, primary cancer of the ocular region. Genetic and epigenetic characteristics of conjunctival melanoma have not been completely elucidated yet. Conjunctival melanoma presents similarities with cutaneous melanoma, with substantial differences in the biological behavior. We reviewed the genetic and epigenetic insights of CjM involved in invasion and metastatic spread. CjM is commonly characterized by mutations of v-raf murine sarcoma viral oncogene homolog B1 ( BRAF ), neurofibromin 1 ( NF1 ) and telomerase reverse transcriptase ( TERT ), high expression of mammalian target of rapamycin (mTOR) and heat shock protein 90 (HSP90), frequent phosphatase and tensin homolog (PTEN) loss and upregulation of specific miRNAs. These features should identify CjM as a distinct subset of melanoma with its own profile, which is more similar to cutaneous melanoma than mucosal melanoma and remarkably different from uveal melanoma., Competing Interests: The authors declare no conflict of interest.

No standard treatment has been established for metastatic uveal melanoma (mUM). Immunotherapy is commonly used for this disease even though UM has not been included in phase III clinical trials with checkpoint inhibitors. Unfortunately, only a minority of patients obtain a clinical benefit with immunotherapy. The immunological features of mUM were reviewed in order to understand if immunotherapy could still play a role for this disease.

Background: No standard treatment has been defined for metastatic uveal melanoma (mUM). Although clinical trials testing Nivolumab/Pembrolizumab for cutaneous melanoma did not include mUM, anti PD-1 agents are commonly used for this disease., Patients and Methods: In this prospective observational cohort single arm study, we investigated efficacy and safety of Pembrolizumab as first-line therapy for mUM. The efficacy was evaluated in terms of progression-free survival (PFS), response rate and overall survival (OS). Toxicity was also assessed., Results: Seventeen patients were enrolled. A median of 8 cycles were administered (range 2-28). Two patients achieved partial response (11.7%), 6 a disease stabilization (35.3%), whereas 9 (53%) had a progression. No complete response was observed. PFS of the overall population was 3.8 months. PFS was 9.7 months for patients with an interval higher than 5 years from diagnosis of primary tumor to metastatic disease and 2.6 months for patients with an interval lower than 5 years [p = 0.039, HR 0.2865 (95% CI 0.0869-0.9443)]. Median OS was not reached. The two responding patients were still on treatment with Pembrolizumab at the time of data analysis. Survival was 12.8 months for patients with clinical benefit, while OS for progressive patients was 3.1 months. PD-L1 expression and genomic abnormalities predictive of relapse after diagnosis of primary tumor were not associated with PFS. Toxicity was mild, without grade 3-4 side effects., Conclusions: The efficacy of Pembrolizumab does not seem particularly different when compared to other agents for mUM, but responding patients had a remarkable disease control.

Purpose: To report the results of a patient's tailored therapeutic approach using a second course of interventional radiotherapy (brachytherapy) in patients with locally recurrent uveal melanoma., Material and Methods: Patients who had already undergone ocular brachytherapy treated at our IOC (Interventional Oncology Center) were considered. Five patients who has received a second course of treatment with a plaque after local recurrences were included in our study. Re-irradiation was performed with Ruthenium-106 (prescribed dose to the apex 100 Gy) or with Iodine-125 plaques (prescribed dose to the apex 85 Gy). Moreover, a systematic literature search was conducted through three electronic databases, including Medline/PubMed, Scopus, and Embase., Results: All patients were initially treated with Ruthenium-106 plaque; the re-irradiation was performed with Ruthenium-106 plaque in three cases and with Iodine in two cases. Mean time between the first and the second plaque was 56.8 months (range, 25-93 months). Local tumor control rate was 100%, no patient underwent secondary enucleation owing to re-treatment failure. Distant metastasis occurred in 1 patient after 6 months from re-treatment. After a median follow-up of 44.2 months (range, 26-65 months) from re-treatment, all patients experienced worsening of the visual acuity (median visual acuity was 0.42 at time of recurrence and decline to 0.24 at the most recent follow-up); cataract occurred in two cases, no patient developed scleral necrosis. We considered 2 papers for a systematic review., Conclusions: In selected cases, especially in presence of marginal local recurrence, a personalized re-treatment strategy with a plaque may offer high probability of tumor control and organ preservation but worsening of visual acuity., Competing Interests: Authors report no conflict of interest.

Background: Traditionally, surgical excision has been the treatment of choice for ocular surface squamous neoplasia (OSSN). Recurrences after surgery are high. To reduce the risk of recurrence, adjuvant therapies have been increasingly used., Purpose: We compared recurrences and complications of 3 forms of treatment for OSSN: surgical excision (group A), surgical excision plus adjuvant topical mitomycin C (MMC) (group B), and surgical excision plus subconjunctival interferon-α-2b (IFN-α-2b) (group C)., Methods: A retrospective comparative study was conducted between January 2006 and March 2016 at the Ocular Oncology Service of the Catholic University of Rome. Seventy-nine patients with a confirmed histological diagnosis of OSSN were included: 43 were treated with surgical excision (group A), 16 underwent surgical excision plus topical MMC (group B), and 20 underwent surgical excision plus adjuvant subconjunctival IFN-α-2b (group C)., Results: The recurrences were different in the 3 groups. Thirty-one recurrences (72%) were seen in group A, 5 (31%) were found in group B, and 3 (15%) were seen in group C. Eight (50%) patients who received MMC 0.02% complained of ocular discomfort, 10 (62.5%) presented conjunctival hyperemia, while conjunctival chemosis and corneal epitheliopathy were noticed in 2 (13%) and 2 (13%) patients, respectively. All patients treated with subconjunctival IFN-α-2b reported flu-like symptoms. Two patients (10%) complained of ocular discomfort., Conclusions: Our study revealed that OSSN is not always manageable with simple excision. Adjuvant chemotherapy is strongly advisable after surgery to reduce recurrences. Interferon injections and MMC drops are effective in preventing recurrences and should be administered after surgery.

Purpose: To investigate how treatment complications are related to dosimetric parameters after ruthenium-106 brachytherapy for uveal melanoma, in a large, clinically homogeneous population., Methods and Materials: A retrospective review was performed to evaluate patients affected by small and medium size uveal melanoma, treated with ruthenium-106 brachytherapy from December 2006 to December 2014. We excluded tumors with posterior margin within 1 mm from the edge of the optic disc and foveola. Main outcome measures were occurrence and time to radiation-related maculopathy, cataract, and optic neuropathy. Secondary end points included local recurrence and distant metastases. Kaplan-Meier analysis with log-rank test and univariate Cox proportional hazards model at 3 years were performed to identify the covariates affecting the outcome of radiation complications., Results: Two hundred thirty-nine patients, with sufficient data to evaluate the end points, were enrolled. Three years after plaque treatment, radiation maculopathy was found in 61 (25.5%) patients, cataract developed in 10 patients (4.2%) receiving a dose of 27 Gy or higher to the lens, and optic neuropathy was observed in 13 patients (5.4%) with an optic nerve dose exceeding 50 Gy and tumor proximity to optic disc of less than 4 mm. Tumor recurrences and tumor-related metastasis were found respectively in 20 (8.36%) and 14 (5.85%) patients., Conclusions: Radiation maculopathy occurs within a median time of 31 months in 25% of cases after plaque treatment for uveal melanoma. The most significant risk factors are total dose and distance of tumor margin from the fovea. If the distance is greater than 11.22 mm, no signs of retinal damage are detected., (Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Although introduced for the treatment of maculopathies, photodynamic therapy (PDT) is now largely used in some eye cancers treatment. The selective tissue damage with PDT is achieved by sequestration of the photosensitizer in the target tissue and focal activation of the photosensitizer by low energy directed light. In this way, it is possible to achieve the destruction of the tumor tissue by safeguarding the surrounding healthy structures. Our study describes the clinical uses and efficacy of photodynamic therapy in ocular oncology., Competing Interests: The authors declare no conflict of interest.

Purpose: To develop a predictive model and nomogram for maculopathy occurrence at 3 years after 106 Ru/ 106 Rh plaque brachytherapy in uveal melanoma., Material and Methods: Clinical records of patients affected by choroidal melanoma and treated with 106 Ru/ 106 Rh plaque from December 2006 to December 2014 were retrospectively reviewed. Inclusion criteria were: dome-shaped melanoma, distance to the fovea > 1.5 mm, tumor thickness > 2 mm, and follow-up > 4 months. The delivered dose to the tumor apex was 100 Gy. Primary endpoint of this investigation was the occurrence of radiation maculopathy at 3 years. Analyzed factors were as follows: gender, age, diabetes, tumor size (volume, area, largest basal diameter and apical height), type of plaque, distance to the fovea, presence of exudative detachment, drusen, orange pigment, radiation dose to the fovea and sclera. Univariate and multivariate Cox proportional hazards analyses were used to define the impact of baseline patient factors on the occurrence of maculopathy. Kaplan-Meier curves were used to estimate freedom from the occurrence of the maculopathy. The model performance was evaluated through internal validation using area under the ROC curve (AUC), and calibration with Gronnesby and Borgan tests., Results: One hundred ninety-seven patients were considered for the final analysis. Radiation-related maculopathy at 3 years was observed in 41 patients. The proposed nomogram can predict maculopathy at 3 years with an AUC of 0.75. Distance to fovea appeared to be the main prognostic factor of the predictive model (hazard ratio of 0.83 [0.76-0.90], p < 0.01). Diabetes (hazard radio of 2.92 [1.38-6.20], p < 0.01), and tumor volume (hazard radio of 21.6 [1.66-281.14], p = 0.02) were significantly predictive for maculopathy occurrence. The calibration showed no statistical difference between actual and predicted maculopathy ( p = 1)., Conclusions: Our predictive model, together with its nomogram, could be a useful tool to predict the occurrence of radiation maculopathy at 3 years after the treatment.

Eye plaque brachytherapy represents a safe and effective therapeutic approach for choroidal melanoma, combining clinical outcomes with an eye and visual preservation. As it represents a complex procedure, a specific quality assurance program is strongly suggested to improve patients and operators safety, and to reduce possible complications linked to surgical procedure and radiation exposure. The aim of this paper is to describe the INTERACTS (Interventional Radiotherapy Active Teaching School) guidelines for quality assurance in choroidal melanoma interventional radiotherapy (brachytherapy) used in our institution., Competing Interests: Authors report no conflict of interest.

Background: A variety of antiinflammatory therapies are employed to promote corneal wound healing. The effects of steroidal and nonsteroidal antiinflammatory drugs on the biomechanical properties of rabbit cornea were investigated over time using tensile tests., Methods: Full-thickness incisions were made and used to analyze the effects of dexamethasone sodium phosphate 0.1% and diclofenac sodium 0.1% on corneal biomechanical properties during wound healing at 7, 14 and 21 days after surgery., Results: The full-thickness incision deeply modified all of the mechanical properties. At 3 weeks after incision, regardless of the drug therapy, the tensile modulus was about 70% of the value for the intact cornea., Conclusions: Topical treatment with dexamethasone was particularly effective during the first week after surgery; the second week after surgery, a similar result was observed in the corneas treated with diclofenac. Low doses of steroidal and nonsteroidal antiinflammatory drugs would seem to have the potential to improve biomechanical properties only during the early stage of the healing process of the cornea.

Purpose: To compare visual outcomes and local tumor control between two groups of patients with amelanotic choroidal melanoma treated with brachytherapy alone, or neoadjuvant photodynamic therapy before brachytherapy., Methods: Patients diagnosed with amelanotic choroidal melanoma were recruited for the study and divided into two groups: brachytherapy alone (Group A) and photodynamic therapy preceding brachytherapy (Group B). Patients of both groups were selected to be comparable., Results: Twenty-six patients with amelanotic choroidal melanoma were enrolled in the study. Within Group B, 1 month after photodynamic therapy, ultrasonography showed reduction of tumor height in 11 patients (73.4%). The mean doses of irradiation to macula and optic nerve, at baseline were 74.37 and 52.07 Gy, whereas after photodynamic therapy there was a decrease of 17.26% (P = 0.008) and 21.22% (P = 0.025), respectively. In terms of visual acuity, a mean decrease of 14 ETDRS letters and 5 ETDRS letters was observed at 24 months follow-up, in Groups A and B, respectively (P = 0.001)., Conclusion: Photodynamic therapy as neoadjuvant therapy before brachytherapy reduces tumor thickness in 73.4% of cases. As a result, a decrease of radiation toxic effects on visual function could be obtained, without compromising disease control.

Purpose: To determine genetic features of a pediatric uveal melanoma in a 6-year-old girl by array-based comparative genomic hybridization (a-CGH) and assess prognosis, and to search for constitutional copy number variations (CNVs) encompassing oncosuppressor genes., Methods: High-resolution a-CGH was performed on genomic DNA from cancer cells and from peripheral blood cells. Histopathology and clinical staging of the tumor were simultaneously assessed., Results: Array-based CGH revealed no CNVs on tumor cells associated with poor prognosis; namely, no monosomy 3, losses of 1p, 6q, or 8p, and no gains of 8q. A unique genomic profile was observed, consisting mainly of partial terminal duplications affecting chromosomes 1, 4, 5, 9, 10, 11, 16, and 19, and complete trisomy of chromosomes 6, 7, and 20. The nonmetastatic tumor had predominantly epithelioid histology. No constitutional CNVs encompassing oncosuppressor genes were detected., Conclusions: We report a very rare uveal melanoma characterized by low-risk genomic profile and poor prognostic histologic and clinical features. The child is relapse-free at 1-year follow-up. The unusual CNVs detected by a-CGH suggest specific pathogenic mechanisms.

Purpose: This study was done to evaluate the role of high-resolution magnetic resonance (MR) imaging with special surface coils in selecting the correct therapeutic approach (eye enucleation or follow-up) in patients with suspected extrascleral extension of uveal melanoma., Materials and Methods: This prospective study involved 12 patients with suspected extrascleral extension of uveal melanoma on orbital ultrasonography. All patients were studied with thin-section MR imaging of the eye using surface coils., Results: High-resolution MR imaging of the eye excluded extrascleral extension of disease in 8/12 patients: in 4/8 cases it revealed vascular ectasia and in the other 4/8 cases the linear hypointensity of the sclera was unbroken. Seven of these eight patients were followed up by ultrasound, which showed stability of melanoma for at least 2 years, while the last patient underwent enucleation, and the histological examination confirmed the MR diagnosis. In 4/12 patients, high-resolution MR suggested a diagnosis of extrascleral extension of melanoma, which was confirmed at histological examination after enucleation., Conclusion: High-resolution MR imaging of the eye with surface coils allowed us to evaluate extrascleral extension of uveal melanoma and choose the correct therapeutic approach, avoiding unnecessary enucleation in 7/12 patients.

Purpose: We sought to examine the clinical features of severe retinopathy of prematurity (ROP) using fluorescein angiography (FA)., Design: Retrospective case series of eyes with severe acute-phase ROP that underwent FA at the time of laser photocoagulation., Participants: We included 22 eyes of 11 infants that developed ROP stage 3 in zone 1 with plus disease, 8 eyes of 4 infants classified as ROP stage 3 in zone 1 without plus disease, and 21 eyes of 11 infants that developed ROP stage 3 in zone 2 with plus disease. All eyes underwent laser photocoagulation. A total of 51 sets of digital images including FA were obtained immediately before treatment., Methods: RetCam (Clarity, Pleasanton, CA) fundus images and video digital FAs were performed under general anesthesia right before laser treatment. A 10% solution of fluorescein was intravenously administered as a bolus at a dose of 0.1 ml/kg, followed by an isotonic saline flush., Main Outcomes Measures: Fluorescein angiograms were examined retrospectively to catalog different retinal and choroidal findings, Results: In eyes with severe ROP, FA clearly shows extreme variability in both retinal circulation and choroidal filling pattern. Different patterns of vessels branching at the junction between vascular and avascular retina (V-Av junction) are noted. Posterior to the V-Av junction, hypoperfused retinal areas with or without hyperfluorescent "cotton-wool-like" or "popcorn-like" lesions due to dye leakage are documented by FA. Focal dilatation of capillaries, capillary tufts formations, and rosary-bead-like hyperfluorescent lesions inside the vessels were seen; sometimes all 3 are noted. Various macular abnormalities are noted including absence of foveal avascular area and significant exudative component., Conclusions: Fluorescein angiography was useful to distinguish the deceptively featureless zone 1 junction between the vascularized and nonvascularized retina. Further studies are needed to understand the role of vascular abnormalities observed in zone 1 vascularized retina., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Clinical examination of the optic nerve and achromatic automated perimetry is the gold standard for the management of glaucoma. However, there is an increasing need for an objective evaluation of the optic nerve structure, particularly for preperimetric glaucoma. Optical coherence tomography (OCT) is a noninvasive tool that measures retinal nerve fiber layer (RNFL) thickness based on its optical properties. Computer image processing algorithms estimate NFL thickness from circumpapillary OCT images that are acquired in cylindrical sections surrounding the optic disc. Average values of NFL thickness can be calculated in the four quadrants or the 12 o'clock position sectors around the optic disc. The mean NFL thickness around the entire disc can also be calculated. NFL thickness values may be compared to a normative database. Although this technique offers objectivity, rapidity, and reproducibility, it is largely influenced by the variability of optic disc size and the number of nerve fibers among individuals. At present, OCT is a good instrument to diagnose early glaucoma, but cannot be used to exclude it. New technologies, like spectral domain and ultra-high resolution, which are already available, will overcome the limitations of OCT.