Multimodal imaging evaluation of combined hamartoma of the retina and retinal pigment epithelium.

PURPOSE: Combined hamartoma of the retina and retinal pigment epithelium is a rare benign tumor characterized by a variable combination of glial, vascular, and pigmented components. The purpose of our study was to analyze the features of combined hamartoma of the retina and retinal pigment epithelium on optical coherence tomography angiography. METHODS: Small case series of two cases of combined hamartoma of the retina and retinal pigment epithelium with macular and optic nerve involvement, evaluated with multimodal imaging including optical coherence tomography, fluorescein angiography, and optical coherence tomography angiography. RESULTS: On optical coherence tomography, combined hamartoma of the retina and retinal pigment epithelium is characterized by disruption of the inner neurosensory retina and a variable degree of involvement of the external retina. Optical coherence tomography angiography showed diffuse alterations of the retinal vessels of the superficial and deeper layers, extended to the peripapillary area. Vessel abnormalities included increased tortuosity and caliber of vessels, vascular traction, and vessel stretching within the lesion. CONCLUSION: Optical coherence tomography angiography allows in-depth multilayer analysis of tumor vascular network, highlighting the fine abnormalities of retinal vasculature characteristic of combined hamartoma of the retina and retinal pigment epithelium.

Morpho-functional evaluation of torpedo maculopathy with optical coherence tomography angiography and microperimetry.

PURPOSE: To report the case of a 13-year-old girl with torpedo maculopathy, evaluated with multimodal morpho-functional retinal imaging, including fundus photography, infra-red and blue fundus autofluorescence, swept-source optical coherence tomography (OCT), en face OCT, OCT angiography and microperimetry (MP). OBSERVATIONS: On fundus examination, a torpedo-like hypopigmented lesion was observed temporal to the fovea in the left eye. OCT showed disruption of outer retinal layers and the presence of a subretinal cleft. On OCTA, a diffuse attenuation of signal from choriocapillaris was observed along the lesion. Functional analysis with MP revealed a reduction of retinal sensitivity over the lesion. CONCLUSIONS: and importance: On OCTA, torpedo maculopathy is characterized by vascular alterations of the choriocapillaris along the lesion.

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.

ARCUATE NERVE FIBER LAYER CHANGES AFTER INTERNAL LIMITING MEMBRANE PEELING IN IDIOPATHIC EPIRETINAL MEMBRANE.

PURPOSE: To analyze the relationship between swelling of the arcuate nerve fiber layer (SANFL) and long-term decrease of retinal nerve fiber layer thickness after internal limiting membrane peeling for idiopathic epiretinal membrane, and to investigate if SANFL is related to a mechanical surgical damage. METHODS: Prospective, interventional consecutive case series of 46 eyes that underwent combined epiretinal membrane/internal limiting membrane peeling for idiopathic epiretinal membrane. Infrared, blue autofluorescence, color fundus imaging and measurement of retinal nerve fiber layer thickness in six peripapillary sectors by spectral-domain optical coherence tomography were performed preoperatively and at 2 weeks, 1, 3, 6, and 12 months after surgery. The presence of SANFL was checked postoperatively on infrared and blue autofluorescence fundus imaging, and the extent of each SANFL was measured on infrared fundus images. RESULTS: Areas of SANFL were identified in 39 eyes (84.8%) at 2-week follow-up. Retinal nerve fiber layer thickness significantly decreased in the temporal sectors at 1, 6, and 12 months (P < 0.0001). The linear extent of SANFL was significantly correlated with the percentage of reduction in retinal nerve fiber layer thickness in the temporal (R = 0.45; P < 0.0001) and infero-temporal (R = 0.23; P = 0.0008) sectors at 12 months of follow-up. Correspondence between sites of surgical grasping and the points of origin of SANFL was demonstrated on blue autofluorescence fundus images superimposed on intraoperative surgical frames. CONCLUSION: Early postoperative SANFL is correlated with late focal retinal nerve fiber layer thinning in the temporal sectors. Intraoperative surgical grasping seems to be a leading factor for the onset of SANFL.

Cisplatin, dacarbazine and vinblastine as first line chemotherapy for liver metastatic uveal melanoma in the era of immunotherapy: a single institution phase II study.

No standard therapy is established for metastatic uveal melanoma. Liver involvement in uveal melanoma may lead to organ impairment, which represents a common cause of death. Tumor shrinkage might improve survival by delaying hepatic failure. Since the combination of cisplatin, vinblastine, dacarbazine allowed a high response rate in metastatic cutaneous melanoma, we explored efficacy and safety of this regimen in unresectable liver metastases of uveal melanoma. In the present phase II study we administered intravenously cisplatin (80 mg/mq, day 1), dacarbazine (250 mg/mq/day, days 1-3), vinblastine (2 mg maximum, day 1) every 21 days as first line treatment for patients with unresectable metastases of uveal melanoma and BRAF wild type. Primary endpoint was objective response rate; overall survival (OS), progression-free survival and toxicity were secondary endpoints. Partial responses were observed in five (20%) patients, stable disease in 12 (48%) patients; disease control rate was 68%. Median OS of all the patients was 13 months, median progression free survival was 5.5 months. OS of responding patients was 21 months; OS of patients with disease control was 18 months, significantly longer than survival of progressing patients (7 months, P=0.0003). Five (20%) patients experienced grade 3-4 toxicity. Combination of cisplatin, vinblastine and dacarbazine was feasible and demonstrate both an interesting objective response rate and a survival benefit for patients achieving a disease control. This regimen could be considered for patients with good performance status and unresectable liver limited disease.

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.

Evaluation of intraorbital injection of rituximab for treatment of primary ocular adnexal lymphoma: a pilot study.

An interventional pilot study to assess the tolerability and activity of the intralesional injection of rituximab, a chimeric mAb that targets the CD20 antigen, in patients with orbital B-cell lymphoma. Five patients received four intralesional injections (one injection a week) of rituximab together with ropivicaine 2%. Side-effects and tumor response were assessed after each injection and during the follow-up (20 months). Two patients obtained complete remission of the intraorbital lesion. Two patients showed incomplete response after induction therapy and received planned escalating rituximab doses, obtaining regression of subjective symptoms. One patient did not achieve tumor regression after the first injection and underwent systemic treatment. This small exploratory study suggests that intralesional rituximab is a well-tolerated treatment for patients with primary ocular adnexal lymphoma. These preliminary findings suggest that intralesional rituximab is a well-tolerated strategy in anterior intraorbital lesion localization of lymphoma.

Photodynamic therapy for vasoproliferative retinal tumors.

PURPOSE: To report our experience with photodynamic therapy (PDT) with verteporfin for patients with vasoproliferative retinal tumors (VPRTs). METHODS: Three patients with VPRTs who presented with macular exudative changes were treated with one session of PDT with 6 mg/m body surface area of verteporfin and a light dose of 100 J/cm at 689 nm delivered in 166 seconds. Biomicroscopy, fluorescein angiography, indocyanine green angiography, optical coherence tomography, and ultrasonography were performed before treatment and 1 month, 3 months, 6 months, and 1 year after treatment; visual acuity was measured using Early Treatment Diabetic Retinopathy Study criteria. RESULTS: At the 1-year follow-up, all tumors responded with a reduction in size (mean height: pretreatment, 2.96 mm; posttreatment, 1.32 mm), and optical coherence tomography showed complete resolution of macular exudates. For all patients, fluorescein angiography evidenced reduction of leakage from the lesion, and indocyanine green angiography verified nonperfusion of the vascular channels. An improvement in visual acuity (average, 4.7 Early Treatment Diabetic Retinopathy Study letters) was observed. No retreatment was needed. CONCLUSION: PDT may represent an effective and safe modality of treatment for VPRTs because of its selectivity. Our study supports the application of a light dose of 100 J/cm, although further studies with larger numbers of cases and longer follow-ups are required.

BIGH3 mutation spectrum in corneal dystrophies.

PURPOSE: To investigate the molecular pathology underlying BIGH3-related corneal dystrophies (CDs) and to further delineate genotype-phenotype specificity. METHODS: Sixty-one index patients with CDs were subjected to phenotypic and genotypic characterization. The corneal phenotypes of all patients were assessed by biomicroscopy and documented by slit lamp photography. The BIGH3 gene was amplified exon by exon from constitutional DNA to perform single-strand conformation polymorphism (SSCP) analysis, followed by direct bidirectional sequencing of abnormal conformers. RESULTS: The phenotypes of CDs were classified as lattice CD in 30 patients, Groenouw type I in 12 (CDGGI), Avellino in 7 (CDA), Reis-Bückler in 8 (CDRB), and Thiel-Behnke in 4 (CDTB). Fifty occurrences of 16 distinct mutations were identified, including 8 novel mutations responsible for lattice type IIIA in three patients (CDLIIA), intermediate type I/IIIA (CDLI/IIIA) in four patients, and atypical CDL with deep deposits in one patient (CDL-deep). CONCLUSIONS: Disease-causing mutations were identified in 80% of the patients (50/61). All mutations localize in two regions of kerato-epithelin: the amino acid R124 and BIGH3 fasc domain 4. This study also confirms the mutation hot spot at positions R124 and R555 with nearly 50% of the mutations targeting these two amino acids (24/50). In addition the corneal phenotypes induced by changes at R124 and R555 are amino acid specific: R124C in CDLI, R555W and R124S in CDGGI, R124H in CDA, R124L in CRRB, and R555Q in CDTB. In CDLIIIA, CDLI/IIIA, and CDL-deep the genotype-phenotype correlation is domain specific, with all changes occurring at the boundary or within the fasc4 domain.