A Prediction Model to Discriminate Small Choroidal Melanoma from Choroidal Nevus.

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.

Patients presenting with metastases: stage IV uveal melanoma, an international study.

OBJECTIVE: To analyse ocular and systemic findings of patients presenting with systemic metastasis. METHODS AND ANALYSIS: It 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. RESULTS: Of 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. CONCLUSIONS: Though 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.

Conjunctival melanoma treatment outcomes in 288 patients: a multicentre international data-sharing study.

BACKGROUND: To relate conjunctival melanoma characteristics to local control. METHODS: Retrospective, registry-based interventional study with data gathered from 10 ophthalmic oncology centres from 9 countries on 4 continents. Conjunctival melanoma patients diagnosed between January 2001 and December 2013 were enrolled in the study. Primary treatments included local excision, excision with cryotherapy and exenteration. Adjuvant treatments included topical chemotherapy, brachytherapy, proton and external beam radiotherapy (EBRT). Cumulative 5-year and 10-year Kaplan-Meier local recurrence rates were related to clinical and pathological T-categories of the eighth edition of the American Joint Committee on Cancer (AJCC) staging system. RESULTS: 288 patients had a mean initial age of 59.7±16.8 years. Clinical T-categories (cT) were cT1 (n=218,75.7%), cT2 (n=34, 11.8%), cT3 (n=15, 5.2%), cTx (n=21,7.3%) with no cT4. Primary treatment included local excision (n=161/288, 55.9%) followed by excision biopsy with cryotherapy (n=108/288, 37.5%) and exenteration (n=5/288, 1.7%). Adjuvant therapies included topical mitomycin (n=107/288, 37.1%), plaque-brachytherapy (n=55/288, 19.1%), proton-beam (n=36/288, 13.5%), topical interferon (n=20/288, 6.9%) and EBRT (n=15/288, 5.2%). Secondary exenteration was performed (n=11/283, 3.9%). Local recurrence was noted in 19.1% (median=3.6 years). Cumulative local recurrence was 5.4% (3.2-8.9%), 19.3% (14.4-25.5%) and 36.9% (26.5-49.9%) at 1, 5 and 10 years, respectively. cT3 and cT2 tumors were twice as likely to recur than cT1 tumours, but only cT3 had statistically significantly greater risk of local recurrence than T1 (p=0.013). Factors such as tumour ulceration, plica or caruncle involvement and tumour thickness were not significantly associated with an increased risk of local recurrence. CONCLUSION: This multicentre international study showed that eighth edition of AJCC tumour staging was related to the risk of local recurrence of conjunctival melanoma after treatment. The 10-year cumulative local recurrence remains high despite current management.

Multicenter, International Assessment of the Eighth Edition of the American Joint Committee on Cancer Cancer Staging Manual for Conjunctival Melanoma.

IMPORTANCE: Eye cancer staging systems used for standardizing patient care and research need to be validated. OBJECTIVE: To evaluate the accuracy of the eighth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual in estimating metastatis and mortality rates of conjunctival melanoma. DESIGN, SETTING, AND PARTICIPANTS: This international, multicenter, registry-based case series pooled data from 10 ophthalmic oncology centers from 9 countries on 4 continents. A total of 288 patients diagnosed with conjunctival melanoma from January 1, 2001, to December 31, 2013, were studied. Data analysis was performed from July 7, 2018, to September 11, 2018. INTERVENTIONS: Treatments included excision biopsy, cryotherapy, topical chemotherapy, radiation therapy, enucleation, and exenteration. MAIN OUTCOMES AND MEASURES: Metastasis rates and 5-year and 10-year Kaplan-Meier mortality rates according to the clinical T categories and subcategories of the eighth edition of the AJCC Cancer Staging Manual. RESULTS: A total of 288 eyes from 288 patients (mean [SD] age, 59.7 [16.8] years; 147 [51.0%] male) with conjunctival melanoma were studied. Clinical primary tumors (cT) were staged at presentation as cT1 in 218 patients (75.7%), cT2 in 34 (11.8%), cT3 in 15 (5.2%), and cTx in 21 (7.3%). There were no T4 tumors. Pathological T categories (pT) were pTis in 43 patients (14.9%), pT1 in 169 (58.7%), pT2 in 33 (11.5%), pT3 in 12 (4.2%), and pTx in 31 (10.8%). Metastasis at presentation was seen in 5 patients (1.7%). Metastasis during follow-up developed in 24 patients (8.5%) after a median time of 4.3 years (interquartile range, 2.9-6.0 years). Of the 288 patients, 29 died (melanoma-related mortality, 10.1%) at a median time of 5.3 years (interquartile range, 1.8-7.0 years). The cumulative rates of mortality among patients with cT1 tumors were 0% at 1 year, 2.5% (95% CI, 0.7%-7.7%) at 5 years, and 15.2% (95% CI, 8.1%-27.4%) at 10 years of follow-up; among patients with cT2 tumors, 0% at 1 year, 28.6% (95% CI, 12.9%-58.4%) at 5 years, and 43.6% (95% CI, 19.6%-77.9%) at 10 years of follow-up; and among patients with cT3 tumors, 21.1% (95% CI, 8.1%-52.7%) at 1 year of follow-up and 31.6% (95% CI, 13.5%-64.9%) at 5 years of follow-up. Patients with cT2 and cT3 tumors had a significantly higher cumulative mortality rate compared with those presenting with cT1 tumors (log-rank P < .001). Patients with ulcerated melanomas had significantly higher risk of mortality (hazard ratio, 7.58; 95% CI, 1.02-56.32; P = .04). CONCLUSIONS AND RELEVANCE: This multicenter, international, collaborative study yielded evidence that the conjunctival melanoma staging system in the eighth edition of the AJCC Cancer Staging Manual can be used to accurately estimate metastasis and mortality rates. These findings appear to support the use of AJCC staging as a tool for patient care and research.

Anterior chamber paracentesis during intravitreal injections in observational trials: effectiveness and safety and effects.

A paracentesis prior to an intravitreal injection is a very safe procedure and can prevent IOP-spikes after injections. As these spikes pose the risk of inducing glaucomatous changes particularly in patients with frequent injections and/or with a risk profile, a regular paracentesis prior to an injection may be considered and discussed with the patient.

TWENTY-FIVE-GAUGE CANNULA-ASSISTED FINE-NEEDLE ASPIRATION BIOPSY OF CHOROIDAL MELANOMA: Cytopathological Analysis.

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.

Autologous Internal Limiting Membrane Fragment Transplantation for Large, Chronic, and Refractory Macular Holes.

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.

Idiopathic polypoidal choroidal vasculopathy masquerading as choroidal tumors: one year follow-up of a peripheral lesion.

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.

Idiopathic polypoidal choroidal vasculopathy masquerading as choroidal tumors: one year follow-up of a peripheral lesion / Vasculopatia polipoidal idiopática da coroide simulando tumores da coroide: um ano de seguimento de uma lesão periférica

ABSTRACT 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.

RESUMO Relato de um caso de vasculopatia polipoidal idiopática da coroide (IPCV) com múltiplas dilatações aneurismáticas em região temporal periférica da retina, em uma paciente idosa que assemelhou-se com alguns tumores de coroide no seguimento de um ano. Paciente de 68 anos da raça negra, assintomática, foi encaminhada com a hipótese diagnóstica de um tumor vascular de coroide e hemangioma capilar da coroide, em região temporal inferior periférica da retina. Ao exame de tomografia de coerência óptica (OCT) era observado dois grande descolamentos de epitélio pigmentado (DEP), sendo confirmado o diagnóstico de vasculopatia polipoidal idiopática da coroide pela angiografia com indocianina verde (ICG). Após um ano, houve absorção do descolamento do epitélio pigmentado hemorrágico assemelhando-se assim ao osteoma de coroide. Nenhum tratamento foi necessário apesar da quantidade dos pólipos. A vasculopatia polipoidal idiopática da coroide é uma doença rara que, dependendo do estágio da apresentação, pode se assemelhar com algumas doenças da coroide. A tomografia de coerência óptica pode ilustrar melhor as características das lesões e a ICG confirma o diagnóstico. Nem todos os casos necessitam ser tratados.

Effect of a single intravitreal bevacizumab injection on contrast sensitivity and macular thickness in eyes with macular edema from central retinal vein occlusion: a prospective, nonrandomized, three-month follow-up study.

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 mm(3)) was reduced significantly at the 1-month (8,324.93 ± 932.04 mm(3)) and 3-month (11,319.44 ± 3,044.74 mm(3)) 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.

VEGF gene polymorphism and response to intravitreal ranibizumab in neovascular age-related macular degeneration.

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.

Radiation therapy: uveal tumors.

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.

Radiation therapy: posterior segment complications.

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.

Contrast sensitivity evaluation in high risk proliferative diabetic retinopathy treated with panretinal photocoagulation associated or not with intravitreal bevacizumab injections: a randomised clinical trial.

PURPOSE: 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). DESIGN: Prospective, randomised, masked, controlled trial. PARTICIPANTS: 42 patients with HR-PDR with visual acuity ≥20/200. METHODS: 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. MAIN OUTCOME MEASURES: Mean change in CS threshold scores between and within groups, from baseline to 6 months. RESULTS: 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 (p>0.05 for all comparisons) between the two groups. In 35 eyes in the control group, compared with baseline values, there was significant worsening (p<0.05) 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. CONCLUSIONS: 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.

Structural and functional assessment of macula in patients with high-risk proliferative diabetic retinopathy submitted to panretinal photocoagulation and associated intravitreal bevacizumab injections: a comparative, randomised, controlled trial.

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.

Intravitreal bevacizumab for type 2 idiopathic macular telangiectasia.

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.

In vitro differentiation of adult adipose mesenchymal stem cells into retinal progenitor cells.

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.

Staining of the internal limiting membrane with the use of heavy brilliant blue G.

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.

Late versus prophylactic chorioretinectomy for the prevention of trauma-related proliferative vitreoretinopathy.

INTRODUCTION: Certain injuries, especially those with a deep-impact (involving the choroid and even the sclera) intraocular foreign body (IOFB), have a high risk for developing either full-blown proliferative vitreoretinopathy (PVR) or full-thickness retinal folds. Although less severe than the former, this so-called 'stage 0 PVR' can severely impact vision, and effective treatment for these folds has not existed heretofore. PATIENTS AND METHODS: Four eyes of 4 patients sustained an IOFB injury with deep impact. All eyes underwent vitrectomy and IOFB removal soon after the injury, and all eyes showed substantial visual improvement postoperatively. However, in a few months the visual acuity dropped again, due to the development of full-thickness retinal folds radiating from the scar. All four eyes then underwent a second vitrectomy with (late rather than prophylactic) chorioretinectomy by creating a 1-mm-wide ring of bare sclera around the scar. The highest setting of the diathermy machine was used as the endodiathermy probe evaporated both the retina and the choroid to create the ring. Laser retinopexy to surround the ring was used only if the lesion was not in the posterior pole. RESULTS: Within a few days, the retinal folds completely disappeared in each eye, and the visual acuity reached the highest earlier value seen after the initial surgery. All patients have long-term follow-up (mean, 22 months) with no postoperative complications. CONCLUSIONS: Chorioretinectomy, although it is ideally used as a prophylaxis against PVR formation and the development of retinal fold formation, also proved equally effective as a late treatment option in the presence of such folds. Such late chorioretinectomy, however, is applicable only for eyes with deep-impact IOFB injuries, not for eyes with a perforating injury or rupture.