Early angiographic signs of retinopathy of prematurity requiring treatment.

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.

Convolutional Neural Network Based on Fluorescein Angiography Images for Retinopathy of Prematurity Management.

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.

Ruthenium brachytherapy for uveal melanomas: Factors affecting the development of radiation complications.

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.

Mitomycin C or interferon as adjuvant therapy to surgery for ocular surface squamous neoplasia: comparative study.

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.

Effect of topical antiinflammatory drugs on mechanical behavior of rabbit cornea.

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.

BRACHYTHERAPY ALONE OR WITH NEOADJUVANT PHOTODYNAMIC THERAPY FOR AMELANOTIC CHOROIDAL MELANOMA: Functional Outcomes and Local Tumor Control.

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.

Unique genomic profile associated with pediatric uveal melanoma.

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.

Atlas of fluorescein angiographic findings in eyes undergoing laser for retinopathy of prematurity.

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.

The role of OCT in glaucoma management.

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.