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Objective: This study aimed to develop a validated machine learning model to diagnose small choroidal melanoma. Design: This is a cohort study. Subjects, Participants, and/or Controls: The training data included 123 patients diagnosed as small choroidal melanocytic tumor (5.0–16.0 mm in largest basal diameter and 1.0 mm–2.5 mm in height; Collaborative Ocular Melanoma Study criteria). Those diagnosed as melanoma (n = 61) had either documented growth or pathologic confirmation. Sixty-two patients with stable lesions classified as choroidal nevus were used as negative controls. The external validation dataset included 240 patients managed at a different tertiary clinic, also with small choroidal melanocytic tumor, observed for malignant growth. Methods: In the training data, lasso logistic regression was used to select variables for inclusion in the final model for the association with melanoma versus choroidal nevus. Internal and external validation was performed to assess model performance. Main Outcome Measures: The main outcome measure is the predicted probability of small choroidal melanoma. Results: Distance to optic disc ≥3 mm and drusen were associated with decreased odds of melanoma, whereas male versus female sex, increased height, subretinal fluid, and orange pigment were associated with increased odds of choroidal melanoma. The area under the receiver operating characteristic “discrimination value” for this model was 0.880. The top four variables that were most frequently selected for inclusion in the model on internal validation, implying their importance as predictors of melanoma, were subretinal fluid, height, distance to optic disc, and orange pigment. When tested against the validation data, the prediction model could distinguish between choroidal nevus and melanoma with a high discrimination of 0.861. The final prediction model was converted into an online calculator to generate predicted probability of melanoma. Conclusions: To minimize diagnostic uncertainty, a machine learning-based diagnostic prediction calculator can be readily applied for decision-making and counseling patients with small choroidal melanoma.

ObjectiveTo analyse ocular and systemic findings of patients presenting with systemic metastasis.Methods and analysisIt is an international, multicentre, internet-enabled, registry-based retrospective data analysis. Patients were diagnosed between 2001 and 2011. Data included: primary tumour dimensions, extrascleral extension, ciliary body involvement, American Joint Committee on Cancer (AJCC)-tumour, node, metastasis staging, characteristics of metastases.ResultsOf 3610 patients with uveal melanoma, 69 (1.9%; 95% CI 1.5 to 2.4) presented with clinical metastasis (stage IV). These melanomas originated in the iris, ciliary body and choroid in 4%, 16% and 80% of eyes, respectively. Using eighth edition AJCC, 8 (11%), 20 (29%), 24 (35%), and 17 (25%) belonged to AJCC T-categories T1–T4. Risk of synchronous metastases increased from 0.7% (T1) to 1.5% (T2), 2.6% (T3) and 7.9% (T4). Regional lymph node metastases (N1a) were detected in 9 (13%) patients of whom 6 (67%) had extrascleral extension. Stage of systemic metastases (known for 40 (59%) stage IV patients) revealed 14 (35%), 25 (63%) and 1 (2%) had small (M1a), medium-sized (M1b) and large-sized (M1c) metastases, respectively. Location of metastases in stage IV patients were liver (91%), lung (16%), bone (9%), brain (6%), subcutaneous tissue (4%) and others (5%). Multiple sites of metastases were noted in 24%. Compared with the 98.1% of patients who did not present with metastases, those with synchronous metastases had larger intraocular tumours, more frequent extrascleral extension, ciliary body involvement and thus a higher AJCC T-category.ConclusionsThough higher AJCC T-stage was associated with risk for metastases at diagnosis, even small T1 tumours were stage IV at initial presentation. The liver was the most common site of metastases; however, frequent multiorgan involvement supports initial whole-body staging.

Objectives: The aim of this paper is to present a diagnostic algorithm for a controversial topic in ophthalmic oncology, small pigmented choroidal tumors ( Material and Methods: Nineteen consecutive patients with a clinical diagnosis of small choroidal pigmented tumors were included in the study. The group of patients studied consisted of 9 patients (47.36%) female and 10 patients (52.64%) male, the age range was 14–68 years. All cases were ophthalmologically evaluated, including best-corrected visual acuity, anterior and posterior segment biomicroscopy, intraocular pressure, binocular indirect ophthalmoscopy, and as additional complementary examinations, ocular ultrasound was performed, which in 100% of the cases was inconclusive, optical coherence tomography, autofluorescence, and angiography in selected cases according to location and symptomatology. In 13 patients (68.50%), transvitreous puncture was performed with or without vitrectomy. Trans-scleral puncture was performed in 6 patients (31.50%), located at the equator (4 patients) and ciliary body (2 patients). Post-surgical follow-up was performed within the first 3 weeks after the procedure and then controlled every 3 months within the 1st year. The material obtained by fine-needle aspiration (FNA) was placed in non-hemolytic preservative liquid. Hematoxylin and eosin, Pas, Masson’s trichrome, and immunohistochemistry (HMB 45, MELAN A, PROT. S-100 base) were performed. Results: The yield of cytologic material was 100% in the sampled patients. The most frequent complication was subretinal hemorrhage in three patients with transvitreous access and two patients with trans-scleral access, in all cases, there was a favorable evolution without requiring further action. In three patients, there were mild vitreous hemorrhages that resolved spontaneously, all of them had undergone transvitreous access. Conclusion: In TPPC of less, we propose a diagnostic algorithm with FNA to obtain cytological sample which allows not only the diagnosis of certainty to indicate treatment but also to determine cytological and molecular prognostic factors that allow classifying melanoma of high or low grade and potentially in case of metastatic disease to indicate systemic treatments. We believe that it is essential to diagnose this type of lesions in which a diagnosis of certainty is required. The alternative is the observation that we consider potentially dangerous in these cases.

PURPOSE To report cytopathological observations on the cells retrieved from the 25-G cannula used during prognostic transvitreal fine-needle aspiration biopsy of choroidal melanoma. METHODS Transvitreal fine-needle aspiration biopsy of choroidal melanoma was performed through a 25-G valved cannula. Twenty samples from 20 consecutive patients were obtained. Most tumors were treated with plaque radiation therapy (16/20, 80%) following standard clinical guidelines. Four enucleated globes (4/20, 20%) were subjected to a similar transvitreal biopsy before enucleation. RESULTS Cytopathological analysis of the cells retrieved from the cannula revealed the absence of any cells in 4 of 20 samples (20%). In the remaining 16 samples, definite melanoma cells and atypical cells (probable melanoma cells) were observed in 2 samples each (total 4, 25%). Histiocytes (4/16, 25%) and lymphocytes (1/16, 6%) were also observed. Thirteen samples (13/16, 81%) contained conjunctival epithelial epithelium. Prognostication could be performed on all fine-needle aspiration biopsy samples (20, 100%). CONCLUSION Use of a 25-G valved cannula offers potential advantages by isolating the needle tract and by allowing retrieval of the contaminating cells without affecting the prognostic yield of the fine-needle aspiration biopsy sample.

Biopsy involves the removal of a tissue sample, laboratory analysis, and interpretation of the results. The usual objective of biopsy has been to establish or confirm a diagnosis. For example, intraocular biopsy is useful when clinical examination fails to distinguish a melanoma from a nevus or metastasis. Even when there is a confident clinical diagnosis, biopsy may be performed to determine the tumor subtype. A uveal tumor can be sampled by aspirational, incisional, or excisional biopsy techniques, depending on its size and location in the eye. Close collaboration with the cytopathologist is essential to ensure adequate sample size and handling. Aspiration biopsy is essentially contraindicated if retinoblastoma is a possibility. In this chapter, we review techniques, indications, complications, and the limitations of intraocular biopsies. Techniques for biopsy of conjunctival, eyelid, and orbital tumors are covered elsewhere in their respective volumes.

The traumatic macular hole is a rare pathology posterior to eye injuries, resulting in loss of visual acuity. It generally affects young men. The pathogenesis of macular hole formation after blunt trauma is today controversial. They frequently appear immediately after the injury, nevertheless in some cases can occur weeks later. The vision usually ranges between 20/80 and 20/400. The exploration typically shows a full-thickness defect of the neurosensory retina at the fovea, elliptical, and with irregular edges. The management can include observation under certain conditions because there is a chance of spontaneous closure. Surgery with vitrectomy obtains the closure of the hole in between 92% and 96% of cases.

Background/Aims: To investigate the association between VEGF gene polymorphism and response to ranibizumab in neovascular age-related macular degeneration (AMD). Methods: A total of 92 patients were genotyped for the VEGF rs1413711 single nucleotide polymorphism. Patients with neovascular AMD initially received 3 monthly ranibizumab intravitreal injections and were retreated as needed. Visual acuity (VA) and central retinal thickness (CRT) were measured before and 1, 3, 6 and 12 months after treatment. Results: For patients with TT and CT genotypes, paired comparisons of mean VA showed improvement when the data obtained at all visits were compared with baseline values, in contrast to patients with the CC genotype. CRT statistically improved at all visits for all genotypes. Conclusion: Patients with the CC genotype showed poorer long-term functional and anatomical response to anti-VEGF therapy.

To compare the effect on contrast sensitivity (CS) measurements of panretinal photocoagulation (PRP) associated with intravitreal bevacizumab (IVB) injections versus PRP alone in high risk proliferative diabetic retinopathy (HR-PDR).Prospective, randomised, masked, controlled trial.42 patients with HR-PDR with visual acuity ≥20/200.Eyes were randomised to one of two groups: one underwent PRP and IVB injections (study group) and the other PRP alone (control group). PRP was performed three times during the study and IVB injection was administered twice.Mean change in CS threshold scores between and within groups, from baseline to 6 months.Seven patients presented with vitreous haemorrhage and were removed from the study. Mean results for CS threshold (at 1.5, 3, 6, 12 and 18 cycles per degree (cpd) frequencies) for patients with and without diabetic macular oedema showed no significant differences (p0.05 for all comparisons) between the two groups. In 35 eyes in the control group, compared with baseline values, there was significant worsening (p0.05) of CS at 1.5, 12 and 18 cpd after 1 month, at 12 cpd after 3 months, and at 6 and 12 cpd after 6 months. In the study group, there was significant improvement in CS at 3 cpd, 3 months after treatment.In eyes with HR-PDR, PRP treatment is associated with deterioration of CS while adjuvant use of bevacizumab prevents such deterioration. CS evaluation seems to support the adjuvant use of bevacizumab when using PRP for the treatment of HR-PDR. ClinicalTrials.gov Identifier NCT 01389505.

Purpose: To compare the efficacy of therapy with panretinal photocoagulation (PRP) and intravitreal bevacizumab (IVB) injections versus PRP alone in patients with high-risk proliferative diabetic retinopathy (HR-PDR) with a 6-month follow-up. Methods: Forty-two patients with HR-PDR were prospectively studied in a randomised, masked, controlled trial. Both eyes of each patient were randomised either to the study group (SG) receiving PRP plus IVB injections or the control group (CG) receiving PRP alone. Mean change in visual acuity (VA), optical coherence tomography-measured foveal thickness (FT) and macular volume (MV) were compared. Results: Intergroup comparisons showed no significant difference in VA while FT exhibited a significant (p < 0.05) difference at 1 month of follow-up and MV was significantly reduced at the 1- and 3-month follow-up. Compared to baseline, VA was significantly worse at all follow-ups in the CG and was stable in the SG. FT increased significantly in the CG from baseline to the 1- and 6-month follow-ups and in the SG, no significant difference was observed. MV was significantly increased in the CG during all follow-up periods. Conclusion: In HR-PDR, using IVB injections as adjuvant treatment to PRP reduces the VA deterioration and results in decreased FT and MV measurements compared to PRP alone.

Purpose To determine the efficacy of liquid-based cytology (LBC) and immunohistochemistry in the evaluation of fine needle aspiration biopsy (FNAB) of intraocular melanocytic tumors. Methods Cytologic diagnosis was necessary in 25 patients with intraocular melanocytic tumors to deliver a therapeutic course of treatment. The patients’ clinical, cytologic, and histologic diagnoses were correlated. All samples were stained with hematoxylin and eosin, and studied through standardized monolayer techniques, with a mean cellular concentration of 60,000 cells/mm2. Immunohistochemistry was performed using Vimentin, S 100, HMB 45, Melan A, cytokeratin, and as prognostic factors, B and T lymphocyte, CD68 (macrophage), and antibody Ki 67 (growth factor). Results The positive predictive value was 100%; the negative predictive value was 80%. Sensitivity and specificity of LBC for detecting malignancy were 95.2% and 100%, respectively. The FNAB LBC with immunohistochemistry findings resulted in a revision of treatment in 32% of patients. There was no evidence of local tumor dissemination or a recurrence associated with biopsy in any patient. Conclusions Fine needle aspiration biopsy (LBC and immunohistochemistry) is a safe, sensitive, and specific method of establishing tissue diagnosis in a subset of patients with intraocular melanocytic tumors, particularly in cases where sample material is scarce. The routine use of immunohistochemical stain increases the diagnostic utility, and prognosis factor determination may change clinical management.

PurposeTo assess of the effect of local recurrence of uveal melanoma on metastasis using a multicenter international tumor registry.DesignRetrospective study using an online tumor registry.ParticipantsPatients with uveal melanoma diagnosed between 2001 and 2011.MethodsA committee was formed to create uveal melanoma patient-specific data fields. Ten subspecialty ophthalmic oncology centers from 4 continents shared data. Patient selection criteria included diagnosis of uveal melanoma and adequate records to allow tumor staging by American Joint Committee on Cancer (AJCC) criteria and follow-up for metastatic melanoma.Main Outcome MeasuresLocal tumor recurrence and metastatic uveal melanoma.ResultsOf 3809 total entries, 3217 patients with ciliary body and choroidal (CBC) melanoma and 160 with iris melanoma were evaluated. There was a median follow-up of 3.7 years (95% confidence interval [CI], 3.5–3.8). One hundred fifty-two patients (4.7%) with CBC melanoma experienced local recurrence, with a cumulative incidence of 11%. Kaplan-Meier point estimates for remaining free of local recurrence were 99% (95% CI, 99–99) at 1 year, 93% (95% CI, 92–94) at 5 years, and 89% (95% CI, 86–91) at 10 years. Five- and 10-year metastasis-free Kaplan-Meier estimates for the recurrence-free group were 87% (95% CI, 86–89) and 82% (95% CI, 79–84), and those for the local recurrence group were 71% (95% CI, 62–78) and 62% (95% CI, 49–72). The difference between these 2 groups was statistically significant (P < 0.001). Furthermore, local tumor recurrence increased the risk of metastasis by a hazard ratio (HR) of 6.28 (95% CI, 4.4–8.9; P < 0.001). Local recurrence was detected up to 9.8 years after treatment. Extrascleral extension also was associated with local recurrence (HR, 3.2; 95% CI, 1.5–6.7; P = 0.003), but higher AJCC T-size category was not (P = 0.63). Five patients (n = 5/161 [3.1%]) with iris melanoma demonstrated local recurrence and 1 metastasized.ConclusionsInternational multicenter data sharing was used to evaluate the effect of local tumor recurrence on metastatic rate. In that local tumor recurrence was associated with a significantly higher risk of systemic metastasis, effective initial treatment and long-term surveillance of treated uveal melanoma patients is necessary.

Although an accurate uveal melanoma staging system is needed to improve research and patient care, the evaluation of eye cancer staging systems requires international multicenter data sharing to acquire a statistically significant analysis.To assess patient mortality outcomes associated with uveal melanoma staging according to the 7th edition of the American Joint Committee on Cancer's AJCC Cancer Staging Manual.A committee was formed to create patient-specific data fields for patients with uveal melanoma. Ten subspecialty ophthalmic oncology centers from 4 continents shared data. Patient selection criteria included diagnosis of uveal melanoma from April 1, 2001, to April 1, 2011, adequate records to allow tumor staging by the AJCC criteria, and follow-up for metastatic melanoma.Primary treatments included local resection, radiation therapy, and enucleation.Metastasis after initial tumor staging with 5- and 10-year Kaplan-Meier metastasis-free point estimates, depending on AJCC prognostic stages I through IV, tumor size category, and subclassification (defined by the presence of ciliary body involvement and/or extrascleral extension).A total of 3809 patients were entered into the database. Of these, 3377 records (88.7%) were complete. Primary ciliary body and choroidal melanoma was the diagnosis for 3217, and 160 had primary iris melanoma. Tumor size categories were T1 in 1115 (34.7%) of the 3217 patients, T2 in 1128 patients (35.1%), T3 in 789 patients (24.5%), and T4 in 185 patients (5.8%). The 5- and 10-year Kaplan-Meier metastasis-free point estimates by tumor size categories were 97% (95% CI, 95%-98%) and 94% (95% CI, 91%-96%) for T1 tumors, 85% (95% CI, 82%-88%) and 80% (95% CI, 75%-84%) for T2 tumors, 77% (95% CI, 73%-80%) and 68% (95% CI, 60%-74%) for T3 tumors, and 61% (95% CI, 49%-71%) (5-year only) for T4 tumors, respectively. Increasing tumor size was consistent with increased metastasis risk (P .001). Subclassifications were significantly associated with increased risk of metastasis (P.001). The AJCC prognostic and anatomical groupings were as follows: stage I, 1030 (32.0%); stage IIA, 1095 (34.0%); stage IIB, 710 (22.1%); stage IIIA, 282 (8.8%); stage IIIB, 79 (2.5%); and stage IIIC, 21 (0.7%). The 5- and 10-year Kaplan-Meier metastasis-free estimates for prognostic stages were 97% (95% CI, 95%-98%) and 94% (95% CI, 91%-96%) for stage I, 89% (95% CI, 86%-91%) and 84% (95% CI, 80%-88%) for stage IIA, 79% (95% CI, 75%-83%) and 70% (95% CI, 62%-76%) for stage IIB, 67% (95% CI, 59%-73%) and 60% (95% CI, 51%-68%) for stage IIIA, 50% (95% CI, 33%-65%) and 50% (95% CI, 33%-65%) for stage IIIB, and 25% (95% CI, 4%-53%) (5-year only) for stage IIIC, respectively. The 160 iris melanomas were too few for subgroup analysis.Multicenter, worldwide, Internet-based data sharing was used to study a heterogenous patient population in ophthalmic oncology. Our results support the continued use of the 7th edition of the AJCCCancer Staging Manual for uveal melanoma.

This case report describes peripheral idiopathic polypoidal choroidal vasculopathy (IPCV) with a collection of small aneurysmal dilations that masqueraded as choroidal tumors in an elderly patient. A 68-year-old African American woman was referred to us with a suspected diagnosis of asymptomatic vascular choroidal tumor and choroidal capillary hemangioma, affecting the temporal peripheral fundus. Upon examination, optical coherence tomography (OCT) revealed two large hemorrhagic pigment epithelium detachments (PED), and indocyanine green angiography (ICG) confirmed the diagnosis of IPCV. One year later, there was reduction in the hemorrhagic pigment epithelium detachments and the lesion took on a different appearance, resembling a choroidal osteoma. No treatment was necessary despite the presence of multiple polyps. IPCV is a rare condition that can resemble other choroidal diseases depending on the stage of presentation. OCT is the best tool to determine the characteristics of the lesions, and indocyanine green angiography should be used to confirm the diagnosis. Not all cases require treatment.

Objective: To evaluate a technique of autologous internal limiting membrane (ILM) fragment transplantation for the treatment of large, chronic, and/or refractory macular holes (MH). Design: This was a 6-month prospective interventional case series. Method: Ten eyes of 10 patients with MH underwent pars plana vitretomy (PPV) and ILM peeling followed by transplantation of an autologous ILM fragment to the MH. Six patients had primary MH with an internal diameter greater than 500 µm and a duration of more than 18 months, including 1 patient with nonproliferative diabetic retinopathy previously treated with panretinal photocoagulation. Four eyes with MH had previously been submitted to PPV (i.e. 1 for retinal detachment and 3 to attempt to close large MH). One of the latter also displayed juxtapapillary choroidal neovascularization due to age-related macular degeneration. The primary and secondary outcomes were MH closure and improvement of the best corrected visual acuity (BCVA), respectively. Results: Complete MH closure was achieved in all cases. A statistically significant improvement in the average BCVA was observed after 6 months of follow-up (p = 0.018; paired t test). The BCVA improved in 8 eyes (80%), and in 6 of those eyes it improved by ≥15 letters. In 1 patient, the BCVA remained unchanged after the surgery, but the visual field reportedly improved. One patient experienced a slight worsening (0.16 logMAR). Two cases developed atrophy of the retinal pigment epithelium despite MH closure and BCVA improvement. Conclusion: Treatment with autologous ILM fragment transplantation seems to be an efficient alternative for large, chronic, and refractory MH.

Fine needle aspiration biopsy (FNAB) of tumors has a long history. The first intraocular biopsy was performed by Hirschberg in 1868. Since the publication of a major report by Jakobiec in 1979, FNAB is increasingly used in the evaluation of ophthalmic tumors. The safety and reliability of ophthalmic FNAB have been reported by several other investigators with adequacy rates of 88–95 %.

Purpose: To evaluate the results of intravitreal bevacizumab (IVB) injection on contrast sensitivity (CS), best-corrected visual acuity (BCVA), foveal thickness (FT) and macular volume (MV) as measured by optical coherence tomography in patients with macular edema (ME) from central retinal vein occlusion (CRVO). Methods: Sixteen consecutive eyes from 16 patients with ME from unilateral CRVO were treated with a single IVB injection. The CS, BCVA, FT and MV measurements were obtained before the treatment and 1 and 3 months after the injection. Results: CS demonstrated significant improvement at all spatial frequencies - 1.5, 3, 6, 12 and 18 cycles per degree (cpd) - 1 month after the injection and at 6 cpd at the 3-month follow-up. The mean BCVA measurements in log of the minimum angle of resolution (logMAR) units improved from 1.03 at baseline to 0.83 logMAR 1 month after the injection, but worsened to 0.97 logMAR at 3 months. The mean baseline FT ± standard deviation (SD; 620.06 ± 177.60 µm) was reduced significantly 1 month (270.93 ± 74.17 µm) and 3 months (535.56 ± 222.33 µm) after the treatment. The mean baseline MV ± SD (12,765.56 ± 3,769.70 mm3) was reduced significantly at the 1-month (8,324.93 ± 932.04 mm3) and 3-month (11,319.44 ± 3,044.74 mm3) follow-up visits. Conclusions: IVB improved CS, BCVA, FT and MV within a short time period (1 month). Although VA was not improved at 3 months, improvements were observed for CS, FT and MV, which indicates that, despite ME recurrence, there still was some benefit to visual function.

Therapeutic radiation to the posterior segment of the eye is a common option for posterior segment tumors. Such tumors are often malignant, but sometimes, benign neoplasms are treated with ionizing radiation. Also, non-neoplastic intraocular lesions like wet age-related macular degeneration may be treated with radiotherapy. Orbital disease, both neoplastic lesions like optic nerve sheath meningioma and non-neoplastic entities like Graves' ophthalmopathy may be treated with radiotherapy and this may include radiation of the optic nerve and posterior segment of the eye. Occasionally, radiotherapy of extraocular malignant disease, involving, e.g. the paranasal sinuses, may cause significant radiation damage to the eye. Complications after radiation to the posterior segment of the eye are largely related to the radiation dose to the posterior segment. The amount of irradiated volume of normal tissue and fractionation are also important for the development of radiation complications to the posterior segment. Radiation retinopathy is the most common complication of the posterior segment, but radiation optic neuropathy also occurs frequently. Radiation scleral necrosis is less frequent probably due to the radioresistance of the scleral collagen. These complications have the potential to cause blindness (radiation retinopathy and optic neuropathy) or enucleation of the eye (scleral necrosis). Although numerous treatments have been advocated, management of radiation-induced damage remains controversial. Efficacy for any treatment still needs to be proven and, if possible, the best option by far is to minimize radiation changes to normal tissue.

Among primary uveal tumors, uveal melanoma is the most frequently occurring malignant neoplasm, albeit much less common than skin melanoma and indeed most other cancers. Traditionally, uveal melanoma was treated by enucleation of the globe, but is now increasingly been managed by an eye-preserving option, which saves vision without compromising the life of patients. More than 90% of eyes now preserved have some form of radiotherapy; most often episcleral brachytherapy that is easily accessible at many ophthalmic centers. Conversely, teletherapy in the form of charged particle irradiation, stereotactic radiotherapy or radiosurgery is only available at a comparatively small number of centers. Radiotherapy for uveal melanoma causes significant side effects and complications, but the vast majority of patients can keep their eye with some remaining function. This is of significant benefit to the quality of life for many patients. The side effects of radiotherapy are intimately related to the size of the irradiated tumor, hence early detection and identification of tumors that need to be treated is critical to improve the functional outcome. Experience gained from treating uveal melanoma has been expanded to treat benign uveal tumors such as choroidal hemangioma and other malignant tumors such as uveal lymphoma and uveal metastasis.

Foreword: Lommatzsch, P.K. Preface: Singh, A.D. Pelayes, D.E. Seregard, S. Macklis, R. * Introduction to Radiotherapy and Standard Teletherapy Techniques: Balagamwala, E.H. Stockham, A. Macklis, R. Singh, A.D. * Teletherapy: Advanced Techniques: Stockham, A. Balagamwala, E.H. Singh, A.D. Macklis, R. * Brachytherapy: Marwaha, G. Macklis, R. Singh, A.D. Wilkinson, A. * Radiation Therapy: Uveal Tumors: Seregard, S. Pelayes, D.E. Singh, A.D. * Radiation Therapy: Retinal Tumors: Sethi, R.V. MacDonald, S.M. Kim, D.Y. Mukai, S. * Radiation Therapy: Age-Related Macular Degeneration: Medina Mendez, C.A. Ehlers, J.P. * Radiation Therapy: Conjunctival and Eyelid Tumors: Aronow, M.E. Singh, A.D. * Radiation Therapy: Orbital Tumors: Marwaha, G. Macklis, R. Singh, A.D. * Radiation Therapy: Anterior Segment Complications: Medina Mendez, C.A. Singh, A.D. * Radiation Therapy: Posterior Segment Complications: Seregard, S. Pelayes, D.E. Singh, A.D. Subject Index.

Se describe un caso de endoftalmitis endógena por nocardia en un varón de 32 años con diagnóstico de lupus eritematoso sistémico. El paciente desarrolló compromiso pulmonar y ocular luego de meses de tratamiento con corticoides y ciclofosfamida. La infección intraocular, de rápida evolución a fístula escleral, recibió tratamiento con vitrectomía, lensectomía y terapia antibacteriana intravítrea y endovenosa. Se aislaron colonias de Nocardia asteroides a partir de material vítreo y aspirado bronquioloalveolar. El ojo afectado evolucionó a ptisis bulbi y fue posteriormente eviscerado, y se realizó el estudio histopatológico.We report a case of endogenous nocardial endophthalmitis in a 32-year-old man with systemic lupus erythematosus. The patient developed pulmonary and ocular disease while on systemic corticosteroid and cyclophosphamide treatment. The intraocular infection progressed to a scleral fistula, and was treatead with pars plana vitrectomy, lensectomy, intravitreous and intravenous antibacterial therapy. The diagnosis of Nocardia asteroides was made by isolation and growth of colonies from samples of a vitreous specimen and bronchioloalveolar aspirates. The eye became phthisical, it was eviscerated, and histopathogical examination was carried out.

Among primary uveal tumors, uveal melanoma is the most frequently occurring malignant neoplasm, albeit much less common than skin melanoma and indeed most other cancers. Traditionally, uveal melanoma was treated by enucleation of the globe, but is now increasingly been managed by an eye-preserving option, which saves vision without compromising the life of patients. More than 90% of eyes now preserved have some form of radiotherapy; most often episcleral brachytherapy that is easily accessible at many ophthalmic centers. Conversely, teletherapy in the form of charged particle irradiation, stereotactic radiotherapy or radiosurgery is only available at a comparatively small number of centers. Radiotherapy for uveal melanoma causes significant side effects and complications, but the vast majority of patients can keep their eye with some remaining function. This is of significant benefit to the quality of life for many patients. The side effects of radiotherapy are intimately related to the size of the irradiated tumor, hence early detection and identification of tumors that need to be treated is critical to improve the functional outcome. Experience gained from treating uveal melanoma has been expanded to treat benign uveal tumors such as choroidal hemangioma and other malignant tumors such as uveal lymphoma and uveal metastasis.

Therapeutic radiation to the posterior segment of the eye is a common option for posterior segment tumors. Such tumors are often malignant, but sometimes, benign neoplasms are treated with ionizing radiation. Also, non-neoplastic intraocular lesions like wet age-related macular degeneration may be treated with radiotherapy. Orbital disease, both neoplastic lesions like optic nerve sheath meningioma and non-neoplastic entities like Graves' ophthalmopathy may be treated with radiotherapy and this may include radiation of the optic nerve and posterior segment of the eye. Occasionally, radiotherapy of extraocular malignant disease, involving, e.g. the paranasal sinuses, may cause significant radiation damage to the eye. Complications after radiation to the posterior segment of the eye are largely related to the radiation dose to the posterior segment. The amount of irradiated volume of normal tissue and fractionation are also important for the development of radiation complications to the posterior segment. Radiation retinopathy is the most common complication of the posterior segment, but radiation optic neuropathy also occurs frequently. Radiation scleral necrosis is less frequent probably due to the radioresistance of the scleral collagen. These complications have the potential to cause blindness (radiation retinopathy and optic neuropathy) or enucleation of the eye (scleral necrosis). Although numerous treatments have been advocated, management of radiation-induced damage remains controversial. Efficacy for any treatment still needs to be proven and, if possible, the best option by far is to minimize radiation changes to normal tissue.

Primary Choroidal Melanoma with Divergent Neuroendocrine Differentiation Background: Despite well-defined histopathological characteristics, melanoma has been reported to have different histological and immunohistochemical variations that can lead to diagnostic controversy. Neuroendocrine divergent differentiation has been demonstrated previously in skin and metastatic melanoma, and also in metastatic tumors to the choroid, but not in primary choroidal melanoma. Aim: To report the clinical, histopathological, immunohistochemical and ultrastructural characteristics of four cases of primary choroidal melanoma with neuroendocrine differentiation. Methods and Results: A retrospective case series analysis was conducted for all patients with choroidal melanoma with confirmed histopathological features of neuroendocrine differentiation, evaluated at the Laboratory of Ophthalmic Research and Visual Sciences. Four cases were identified, two male and two female. Preoperative clinical diagnosis was choroidal melanoma for all cases. Atypical small-cell morphology distributed in a pattern forming an organoid, perivascular or nested architecture on light microscopy was found in all cases, which prompted further evaluation with neuroendocrine markers. Immunohistochemistry demonstrated positivity in at least three melanocytic and three neuroendocrine markers for each case. Hi-resolution optic microscopy showed granules corresponding to intracytoplasmic neurosecretory and melanin granules in the same cells, confirming the diagnosis. Conclusions: In this study we provide evidence suggestive of divergent neuroendocrine differentiation in primary choroidal melanoma.

Introduction: It has been previously shown that adult mesenchymal stem cells (MSCs) differentiate into neural progenitor cells (NPCs) and that the differentiation process was completed in 24–48 h. In this previous study, MSCs from a bone marrow or fat source were co-incubated with homologous autoaggressive cells (ECs) against nerve tissue, and these NPCs were successfully used in human regenerative therapeutic approaches. The present study was conducted to investigate whether a similar differentiation method could be used to obtain autologous retinal progenitor cells (RPCs). Methods: Human Th1 cells against retinal tissue were obtained by challenging human blood mononuclear cells with an eye lysate of bovine origin; negative selection was performed using a specific immunomagnetic bead cocktail. Fat MSCs were obtained from a human donor through mechanical and enzymatic dissociation of a surgical sample. The ECs and MSCs were co-cultured in a serum-free medium without the addition of cytokines for 0, 24, 48 and 72 h. The plastic adherent cells were morphologically examined using inverted-phase microscopy and characterized by immunofluorescent staining using antibodies against Pax 6, TUBB3, GFAP, Bestrophin 2, RPE 65, OPN1 SW, and rhodopsin antigens. Results: The early signs of MSC differentiation into RPCs were observed at 24 h of co-culture, and the early differentiated retinal linage cells appeared at 72 h (neurons, rods, Müller cells, retinal ganglion cells and retinal pigmented epithelial cells). These changes increased during further culture. Conclusion: The results reported here support the development of a method to obtain a large number of autologous adult RPCs, which could be used to treat different retinopathies.

Background: Brilliant blue G (BBG) is frequently used in chromovitrectomy to facilitate internal limiting membrane (ILM) peeling. A study was initiated to evaluate if heavy BBG is safe and effective in staining the ILM. Methods: We studied 30 eyes, 23 with idiopathic macular holes and 7 of patients with diabetic macular edema. Removal of the ILMs was assisted by heavy BBG staining. In cases with histopathological correlation the ILMs were evaluated with hematoxylin and eosin, Masson’s trichrome, periodic acid-Schiff and glial fibrillary acidic protein staining. In addition, immunohistochemistry was also performed using specific antibodies for vimentin, neuron-specific enolase, factor VIII and CD68. Using the Image-Pro Plus software of Media Cybernetics Co. we found an average thickness in ILMs. Results: Of the ILM specimens sent, 19/30 (63.33%) could not be processed properly because of the limited sample material, recognizing only fragments of dispersed fibrillar material. In macular hole ILMs we found an average thickness of 1.3 ± 0.65 µm, and in diabetic macular edema ILMs an average thickness of 6.2 ± 1.4 µm. Conclusions: In heavy BBG-assisted ILM peeling we observed no intraoperative or postoperative complications after a mean follow-up of 12 months. Heavy BBG could be an effective and safe vehicle for staining the ILM.

Background/Aims: The aim of this paper is to report the treatment of type 2 nonproliferative idiopathic macular telangiectasia (IMT) with intravitreal bevacizumab (IVB). Methods: Retrospective case series of 10 eyes of 5 patients with type 2 IMT. All patients received 3 monthly IVB injections. Visual acuity (VA), fluorescein angiography (FA) and optical coherence tomography (OCT) were performed at baseline and 4 weeks after each injection. Results: Four weeks after the third IVB injection, VA remained stable for all patients. All eyes showed some decrease in fluorescein leakage, and there was a mild decrease in central macular thickness. One year later, VA, OCT and FA findings returned to the baseline levels. Conclusion: IVB did not improve VA in cases of type 2 IMT.

Classically, the diagnosis of intraocular tumors (IOT) was done through noninvasive methods, nevertheless diverse situations of presentation of IOT like previous treatment, unusual clinical presentati

Purpose Panphotocoagulation reduces the risk of vision loss in proliferative diabetic retinopathy. However, not many patients tolerate this treatment well due to pain. Therefore, we evaluated the analgesic effect of etoricoxib during photocoagulation in patients with proliferative diabetic retinopathy. Methods A prospective, randomized, double-blind study was conducted on 44 consecutive patients eligible for panphotocoagulation due to proliferative diabetic retinopathy. During the first panphotocoagulation session, both groups were treated without medication. During the following session, the control group received a placebo pill while the other group received etoricoxib 120 mg. Both groups took the medicines 1 hour before the treatment. After each session, the patients quantified the level of pain on a subjective visual scale. Results A total of 52 patients were selected for the study and the data of 44 patients were analyzed. In the control group, the average level of pain in the first session was 7.68 (standard deviation 1.70), dropping to an average of 7.32 (standard deviation 1.39) after ingestion of placebo. Therefore, there was no statistical difference (p=0.1187). In contrast, the average level of pain without the drug in the group taking etoricoxib 120 mg was 7.95 (standard deviation 1.46) vs 5.18 (standard deviation 1.65) with the drug, a significant statistical difference (pConclusions Etoricoxib 120 mg reduces pain and can be used before panphotocoagulation. Data show that the medication is more effective against pain during photocoagulation than placebo.

Purpose TO report the optical coherence tomographic features differentiating choroidal nevus from choroidal melanoma by 3D spectral-domain optical coherence tomography (SD-OCT) and OCT characteristics of other choroidal tumors. Methods A total of 67 consecutive eyes with choroidal tumors including choroidal nevus (25 eyes), indeterminate choroidal melanocytic lesion (11 eyes), malignant melanoma (23 eyes), metastasis (4 eyes), hemangioma (2 eyes), and osteoma (2 eyes) were imaged with 3D SD-OCT (OCT-1000; Topcon Inc., Paramus, NJ). The images were analyzed for the presence or absence of SD-OCT findings such as retinal pigment epithelium (RPE)/choriocapillaris reflectivity, RPE irregularity, drusen, sub-RPE fluid, RPE thickness, subretinal deposit, subretinal fluid, intraretinal edema, retinal thickness, and photoreceptor inner and outer segment junction (IS/OS). Visualization of the choroidal tumor and its intrinsic reflectivity OCT features were also assessed. Results When compared with nevus, subretinal deposit, subretinal fluid, and intraretinal edema were detected significantly more frequently in the eyes with malignant melanoma (pConclusions SD-OCT provides useful information to observe and document the retinal and RPE changes secondary to choroidal tumors that help differentiate choroidal nevus from malignant melanoma. Improvements in the current OCT systems are needed to better characterize intrinsic features of choroidal tumors.

Purpose. To evaluate the change in vision after 3 monthly consecutive intravitreal injections of 1.25 mg of bevacizumab for neovascular age-related macular degeneration (AMD). Methods. A retrospective analysis of 35 eyes was performed. Visual acuity (VA) at initial visit and at each follow-up visit was compared. The injection of bevacizumab was performed at 30-day intervals and patients were observed for 5 months after the last injection. Results. Of the 35 eyes, 9 had received previous treatment with photodynamic therapy with or without 4 mg of intravitreal triamcinolone. VA was measured in Snellen table and transformed into logMAR for statistical purposes. Mean age was 76.66 years (range, 49–90 years). There were 24 (69%) women and 11 (31%) men. Mean VA at the initial visit was 0.92±0.50. At month 1, mean VA was 0.84±0.51 and at month 2 was 0.74±0.51. At month 3, mean VA remained 0.74±0.49. Six and 8 months after the initial visit, VA was 0.79±0.49 and 0.77±0.50, respectively. The improvement in VA was statistically significant at month 2 and at the end of the follow-up (8 months) compared with the baseline VA. Conclusions. Three consecutive monthly injections of intravitreal bevacizumab to treat neovascular AMD is effective in improving VA in the short term. Longer prospective studies should be performed to confirm VA stability after the third injection.

espanolObjetivo/metodo: Se presenta un raro tumor con ubicacion conjuntival, un colagenoma de celulas gigantes. Se exponen las caracteristicas histopatologicas utilizando Hematoxilina y Eosina, PAS, Tricromico de Masson e inmunohistoquimica. Resultados/conclusiones: Se presentan las caracteristicas clinicas e histopatologicas del colagenoma de celulas gigantes de conjuntiva, que son similares a las caracteristicas de este tumor en otras partes del cuerpo. Este es el primer reporte de este tumor en el ojo. EnglishPurpose/methods: To report a rare case of a tumor in a conjunctival location, a giant cell collagenoma. Tissue was stained with hematoxylin-eosin, periodic acid-Schiff, and Masson’s trichromic stain and studied by immunohistochemistry. Results/conclusion: The clinical and histopathologic features of conjunctival giant cell collagenoma are similar to characteristics of the same tumor occurring in other parts of the body. This is the first report of this tumor in the eye.

We report a case of endogenous nocardial endophthalmitis in a 32-year-old man with systemic lupus erythematosus. The patient developed pulmonary and ocular disease while on systemic corticosteroid and cyclophosphamide treatment. The intraocular infection progressed to a scleral fistula, and was treated with pars plana vitrectomy, lensectomy, intravitreous and intravenous antibacterial therapy. The diagnosis of Nocardia asteroides was made by isolation and growth of colonies from samples of a vitreous specimen and bronchioloalveolar aspirates. The eye became phthisical, it was eviscerated, and histopathogical examination was carried out.

espanolObjetivo/metodo: Presentar los hallazgos anatomo-patologicos de un caso de cilio intravitreo asociado a pucker macular. Se relacionan con factores clinicos para establecer el tratamiento. Se realiza vitrectomia por pars plana y pelado de la membrana prerretiniana. Se extraen piezas quirurgicas que son estudiadas con Hematoxilina y Eosina, PAS, Tricromico de Masson e inmunohistoquimica. Resultados/conclusiones: El examen histopatologico informo la presencia de cilio con una capa cuticular rodeandolo parcialmente y membrana limitante interna con gran aumento de la celularidad. En aquellos casos en los cuales el cilio intraocular se asocia a otro tipo de patologia de resolucion quirurgica o cuando produce trastornos inflamatorios o alteracion visual, esta indicada la extraccion quirurgica. EnglishPurpose/methods: To report the pathological findings in a case of intravitreous cilia with macular pucker. We considered clinical factors to establish treatment. A pars plana vitrectomy and premacular membrane peeling were performed. Surgical samples were removed and studied with PAS, hematoxylin-eosin, Masson’s Trichromic and immunohistochemistry. Results/conclusion: The histopathological examination disclosed the presence of cilia partially surrounded by a cuticle layer and internal limiting membrane with a celullarity increase. Surgical extraction is indicated in those cases in which the intraocular cilia are associated with any surgically treatable process or when it produces ocular inflammation or visual disturbance.

In a great majority of cases, uveal tumours are diagnosed and treated based solely upon clinical examination and ancillary diagnostic studies such as ultrasonography and angiography.1 In general, diagnostic fine needle aspiration biopsy (FNAB) is limited to situations presenting as a diagnostic dilemma such as differentiation between an amelanotic uveal melanoma and a metastatic uveal tumour.2–5 The other major indication for ophthalmic FNAB is for prognostication purposes of uveal melanoma being treated with radiation therapy.6 Most ophthalmic surgeons have used available needles without customisation ranging in size from 22 gauge (G) to 30G, with the 25G needle being the most commonly used.2 ,7 , …

Rupture is the most severe form of mechanical globe trauma because of the tissue pathologies that occur at the time of injury and because of the post-injury destruction caused by scar formation as part of the body’s normal healing process. The diagnosis is usually straightforward because the wound is visible, often even to the naked eye. However, occult scleral ruptures – conjunctival integrity preserved – are not uncommon; any injury resulting from an impact by a large, blunt object therefore requires careful ocular evaluation. Due to the risk of expulsive choroidal haemorrhage wound closure is typically urgent, but all rules of proper wound toilette and suturing must be followed. The surgeon may elect to perform a staged approach, in which the initial wound-closure surgery is followed by intense topical corticosteroid therapy and then a second, comprehensive intraocular reconstruction a few days later, or to perform primary comprehensive surgery. All tissue pathologies must be properly addressed by an expert ocular traumatologist; in eyes with posterior scleral rupture, prophylactic chorioretinectomy should also be considered.