In vivo study to assess dosage of allogeneic pig retinal progenitor cells: Long-term survival, engraftment, differentiation and safety.

Despite notable efforts and significant therapeutical advances, age-related macular degeneration remains the single most common reason for vision loss. Retinal progenitor cells (RPCs) are considered promising candidates for cellular treatments that repair and restore vision. In this allogenic study, the phenotypic profile of pig and human RPCs derived using similar manufacturing processes is compared. The long-term (12-week) survival of green fluorescent protein-pig retinal progenitor cells GFP-pRPC after subretinal transplantation into normal miniature pig (mini-pig) retina is investigated. Human eyes are both anatomically and physiologically mimicked by pig eyes, so the pig is an ideal model to show an equivalent way of delivering cells, immunological response and dosage. The phenotypic equivalency of porcine and clinically intended human RPCs was established. Thirty-nine mini-pigs are used in this study, and vehicle-injected eyes and non-injected eyes serve as controls. Six groups are given different dosages of pRPCs, and the cells are found to survive well in all groups. At 12 weeks, strong evidence of integration is indicated by the location of the grafted cells within the neuro-retina, extension of processes to the plexiform layers and expression of key retinal markers such as recoverin, rhodopsin and synaptophysin. No immunosuppression is used, and no immune response is found in any of the groups. No pRPC-related histopathology findings are reported in the major organs investigated. An initial dose of 250 k cells in 100 µl of buffer is established as an appropriate initial dose for future human clinical trials.

A bullous variant of central serous chorioretinopathy treated with oral spironolactone.

We report the case of a 39-year-old male patient who presented with visual loss in the right eye for 6 weeks. The best-corrected visual acuity was counting fingers in the right eye and 20/30 in the left eye. The fundus examination demonstrated a right retinal detachment inferiorly extending to the fovea and a left macular serous detachment. After multimodal imaging study, the patient was diagnosed as having a bullous variant of central serous chorioretinopathy and treated with oral spironolactone associated with adjuvant laser photocoagulation. The retinal changes resolved after 6 months. The final visual acuity was 20/20 in both eyes.

Pseudophakic macular edema in nondiabetic and diabetic patients without diabetic retinopathy treated with intravitreal dexamethasone implant.

BACKGROUND: The purpose of this study was to compare the impact of intravitreal dexamethasone (DEX) implant during a 12-month period in nondiabetic and diabetic patients without diabetic retinopathy (DR) as a treatment for refractory pseudophakic cystoid macular edema (PCME) following prior treatment with topical nepafenac 0.1% and prednisolone 1%. METHODS: Forty-two consecutive medical records of patients diagnosed with PCME after uneventful cataract surgery were included. The outcomes measured included best corrected visual acuity (BCVA) and central foveal thickness (CFT). Linear regression analysis was statistically applied. RESULTS: Following topical treatment, nondiabetic and diabetic subjects presented a mean ± SD gain of - 0.11 ± 0.11 and - 0.18 ± 0.11 BCVA logMAR and a CFT reduction of - 43.42 ± 53.66 µm and - 58.76 ± 36.28 µm, respectively. The mean BCVA gain at month 12 subsequent to DEX implantation was - 0.35 ± 0.17 in nondiabetic (p < 0.001) and - 0.55 ± 0.26 in diabetic patients (p < 0.001), with CFT reductions of - 195.71 ± 93.23 µm (p < 0.001) and - 260.81 ± 198.69 µm (p < 0.001), respectively. Patients who responded with better VA after topical treatment presented better visual outcomes at month 12 following DEX implantation (r2 = 0.46; rho = - 0.71, p < 0.01). CONCLUSION: Nondiabetic and diabetic patients without DR demonstrated similar results after DEX implant after combined topical therapy, suggesting that selected diabetic patients may have a response comparable to that of nondiabetic patients with PCME.

Multimodal imaging in a patient with combined hamartoma of the retina and retina pigment epithelium.

Combined hamartoma of the retina and retinal pigment epithelium is a rare, benign intraocular tumor. Hamartoma of the retina and retinal pigment epithelium has been described in the literature as a condition presenting with variable retinal damage, ranging from partial epiretinal involvement to complete distortion of the retinal layers and retinal pigment epithelium. We report the case of an 8-year-old girl presenting with longstanding strabismus who was diagnosed with Hamartoma of the retina and retinal pigment epithelium based on multimodal imaging assessment. We explored the particular imaging findings from studies using spectral-domain optical coherence tomography, fundus autofluorescence, optical coherence tomography angiography, and fluorescein angiography.

Analysis of cytokines in the aqueous humor during intravitreal Ranibizumab treatment of diabetic macular edema.

This study aimed to analyze the concentrations of VEGF, b-FGF, TNF, interleukin (IL)-1, IL-6, IL-8, IL-10, and IL-12 in the aqueous humor of patients with diabetic macular edema with and without peripheral retinal ischemia and to ascertain the changes in the levels of these molecules during treatment with ranibizumab. A therapeutic, prospective, randomized interventional study was carried out. Twenty-four eyes from 24 patients were studied and divided into 3 groups. Group 1 (9 eyes) included patients with diabetic macular edema without peripheral ischemia. Group 2 (10 eyes) included patients with diabetic macular edema with peripheral ischemia. Group 3 (5 eyes), the control group, included patients without systemic and/or eye diseases. Patients in Groups 1 and 2 received 3 intravitreal injections of 2 mg/0.05 ml ranibizumab at an interval of approximately 30 days. Before administering the injections, the aqueous humor was collected. In the control group, aqueous humor was collected before facetectomy. During treatment, the median IL-6 concentration significantly increased in Group 1 but showed a slight but not significant decrease in Group 2. Interleukin 8 levels were significantly different at the end of treatment compared to the beginning in Groups 1 and 2. TNF, IL-1, IL-10, and IL-12 levels were practically unchanged in both groups. VEGF was significantly reduced at the end of the study in Groups 1 and 2. B-FGF was not detected in most of the studied patients, and in those with detectable levels, there was no significant variation. There was a significant increase in the median level of interleukin 6 in the group without ischemia and a significant decrease in VEGF in both groups. The cytokines TNF, IL-1, IL-10, and IL-12 did not show significant variation.

Retinal ischemia following mandible tumor treatment with steroid injection.

Central giant cell granuloma is a rare osseous tumor affecting young patients with anatomical and functional compromise of the maxilla and mandible. Steroid injection therapy constitutes a less invasive treatment modality for disease control in selected cases. Retinal ischemia is a reported complication of multiple medical procedures, including dental interventions, and may lead to loss of vision with poor prognosis. We report a case of retinal arteriolar ischemic disease following central giant cell granuloma management with local injected corticosteroids.

Pedicle internal limiting membrane flap technique for very large macular holes: a preliminary report.

BACKGROUND: Conventional vitrectomy technique for macular hole surgery has a good outcome in small and medium macular holes, but for very large macular holes (minimum linear diameter higher than 700 µm) other techniques were developed aiming to achieve greater rates of closure and visual acuity gain. The purpose of this article is to report the anatomical and functional outcomes of four very large macular hole (MH) cases which have undergone vitrectomy with the pedicle internal limiting membrane (ILM) flap technique. METHODS: This is a retrospective series of four patients with large MH who were treated with vitrectomy and the pedicle ILM flap technique. Comprehensive ophthalmologic evaluation was performed before surgery and included ETDRS best-corrected visual acuity (BCVA) and spectral domain optical coherence tomography (SD-OCT) for MH measures: height, minimum linear diameter (MLD) and external base diameter. The particular detail of this technique is related to ILM flap creation. During the peeling, the ILM was not removed completely from the retina but was left attached to the edges of the macular hole and subsequently trimmed with the vitrectomy probe using the scissors mode. RESULTS: Four patients with very large MH underwent PPV and the pedicle ILM flap technique was used to pursue macular closure. Median preoperative BCVA was 20/400 (range: 20/320 to 20/400) and median postoperative BCVA was 20/200 (range: 20/320 to 20/200). Of the 4 cases reported, 3 obtained anatomical closure (75%), and also presented BCVA improvement after surgery, considering the last follow-up visit of each case. No additional procedures were performed in either case. One patient demonstrated no anatomic and functional improvement. CONCLUSION: The present study describes the first Brazilian case series of very large MH treated by the inverted pedicle ILM flap technique. This technique was associated with anatomic and visual improvement in most cases, and represents an alternative therapeutic approach for large macular holes.Trial Registration Project registered in Plataforma Brasil with CAAE number 30163520.0.0000.5440 and approved in ethics committee   from  Ribeirão Preto Medical School Clinics Hospital, University of São Paulo-Ribeirão Preto, São Paulo, Brazil (appreciation number 3.948.426 gave the approval).

Surgical results regarding the correction of macular hole with and without face-down posturing using 25% SF6 gas: a retrospective case series.

PURPOSE: This study aims to compare the anatomical success rates of vitrectomy and SF6 gas tamponade for macular hole surgery with and without postoperative face-down posturing. METHODS: This was an observational, longitudinal, and retrospective case series analysis. The study included 52 eyes from 52 patients who underwent pars plana vitrectomy with trypan blue-assisted internal limiting membrane peeling and 25% SF6 tamponade for stages 2, 3, and 4 macular holes. After surgery, all patients were provided with a postoperative postural regimen: 31 patients were instructed not to maintain face-down posturing, whereas 21 were instructed to maintain face-down posturing for 7 days. The primary outcome measure was the macular hole closure rate. Statistical analysis was performed using Epi Info 7.1. RESULTS: A total of 47 (90.3%) patients achieved hole closure. The nonface-down posturing group and face-down posturing group obtained closure rates of 90.3% and 90.4%, respectively; these rates were not significantly different. Statistical analysis revealed that no significant differences existed in sex, age, hole duration, hole stage, preoperative visual acuity, or postoperative visual acuity between the two groups. CONCLUSION: Our results suggest that macular hole surgery with the use of short duration gas (SF6) is safe and effective and that maintaining a postural orientation of nonface-down posturing is also safe. However, these recommendations should be assessed further in a prospective and randomized study to comprehensively delineate the associated benefits and risks.

Oct angiography compared to fluorescein angiography, indocyanine green angiography and optical coherence tomography in the detection of choroidal neovascularization in pigment epithelial detachment.

PURPOSE: To evaluate the agreement between multimodal imaging-MI (fluorescein angiography, indocyanine green angiography, optical coherence tomography) and optical coherence tomography angiography (OCTA) in the detection of choroidal neovascularization (CNV) in patients with pigment epithelial detachment with subretinal/intraretinal fluid (PED+F) compared to patients with PED without subretinal/intraretinal fluid (PED-F). METHODS: Twenty-two eyes of 15 patients were divided into two groups (PED+F and PED-F). All patients underwent MI and OCTA with manual and automatic segmentation. MI findings were compared to OCTA findings and then analysed. RESULTS: In the PED+F group (10 eyes), all studied eyes demonstrated CNV in MI. In manual segmentation OCTA assessment, 9 of 10 eyes (90%) were detected with CNV. When evaluated by automatic segmentation, 8 of 10 eyes (80%) revealed the presence of CNV. In the PED-F (12 eyes) group, all eyes did not demonstrate CNV in MI and OCTA evaluations, either by manual or automatic segmentation. The agreement between MI and OCTA shows concordance (k: 0.908; 95% CI, 0.491-1.000); the evaluation of the agreement between the automatic and manual segmentation also shows concordance (k: 0.904; 95% CI, 0.488-1.000). CONCLUSION: The solid agreement between the multimodal imaging regarding the ability of OCTA to identify possible initial CNV in a patient with PED-F was observed. Accuracy was 95.45%. In addition, the agreement between manual and automatic segmentation to identify CNV on OCTA was also shown.

In vivo and in vitro toxicity evaluation of liposome-encapsulated sirolimus.

BACKGROUND: To evaluate the in vivo and in vitro toxicity of a new formulation of liposome-encapsulated sirolimus (LES). METHODS: In vitro experiments were done using ARPE-19 and HRP cells. An MTT assay was used to determine cell metabolic activity and a TUNEL assay for detecting DNA fragmentation. In vivo experiments were conducted on New Zealand albino rabbits that received intravitreal injections of empty liposomes (EL) or different concentrations of LES. Histopathological and immunohistochemical analyses were performed on the rabbit's eyes following injection. RESULTS: Eighteen eyes of nine rabbits were used. MTT assay cell viability was 95.04% in group 1 (12.5 µL/mL LES). 92.95% in group 2 (25 µL/mL LES), 91.59% in group 3 (50 µL/mL LES), 98.09% in group 4 (12.5 µL/mL EL), 95.20% on group 5 (50 µL/mL EL), 98.53% in group 6 (50 µL/mL EL), and 2.84% on group 8 (50 µL/mL DMSO). There was no statistically significant difference among groups 1 to 7 in cell viability (p = 1.0), but the comparison of all groups with group 8 was significant (p < 0.0001). The TUNEL assay comparing two groups was not statistically significant from groups 1 to 7 (p = 1.0). The difference between groups 1 to 7 and group 8 (p < 0.0001) was significant. Histopathological changes were not found in any group. No activation of Müller cells was detected. CONCLUSION: A novel formulation of LES delivered intravitreally did not cause in vitro toxicity, as evaluated by MTT and TUNEL assays, nor in vivo toxicity as evaluated by histopathology and immunohistochemistry in rabbit eyes.

A bullous variant of central serous chorioretinopathy treated with oral spironolactone / Uma variante bolhosa da coriorretinopatia serosa central tratada com espironolactona oral

ABSTRACT We report the case of a 39-year-old male patient who presented with visual loss in the right eye for 6 weeks. The best-corrected visual acuity was counting fingers in the right eye and 20/30 in the left eye. The fundus examination demonstrated a right retinal detachment inferiorly extending to the fovea and a left macular serous detachment. After multimodal imaging study, the patient was diagnosed as having a bullous variant of central serous chorioretinopathy and treated with oral spironolactone associated with adjuvant laser photocoagulation. The retinal changes resolved after 6 months. The final visual acuity was 20/20 in both eyes.

RESUMO Relatamos o caso de um homem de 39 anos apresentando perda visual no olho direito há seis semanas. A melhor acuidade visual corrigida foi conta-dedos no olho direito e 20/30 no esquerdo. A fundoscopia demonstrou descolamento de retina direito inferiormente com extensão à fóvea e descolamento macular seroso à esquerda. Após estudos de imagem multimodal, o paciente foi diagnosticado com uma variante bolhosa de coriorretinopatia serosa central e tratado com espironolactona oral associada à fotocoagulação a laser adjuvante. As alterações retinianas resolveram após seis meses. A acuidade visual final foi 20/20 em ambos os olhos.

Retinal changes in rabbit after intravitreal injection of sunitinib encapsulated into solid lipid nanoparticles and polymeric nanocapsules.

PURPOSE: We aimed to evaluate the safety of single intravitreal injection of each of two concentrations of 0.1 ml of sunitinib (1 and 10 mg/ml), 0.1 ml of a drug-free dispersion containing solid lipid nanoparticles, and 0.1 ml of a drug-free dispersion containing polymeric nanocapsules for analyzing the possible toxic effects using electrophysiology and histology in albino rabbit retina. METHODS: We conducted an experimental controlled study of 20 eyes of albino rabbits. Intravitreal injections of each specific agent were applied to one eye per rabbit in each 5-rabbit group, while the contralateral eyes received no treatment and were used as controls. RESULTS: We noted no electroretinographic changes in the sunitinib (1 and 10 mg/ml) or in solid lipid nanoparticles groups. However, we observed significant abnormalities in ocular morphology and in the electroretinogram in the nanocapsules group. At the histological level, only the nanocapsules group demonstrated abnormal changes, including severe edema and cytoplasmic vacuole formation. CONCLUSIONS: While nanocapsules intravitreal injections indicated retinal toxic effects, sunitinib and solid lipid nanoparticles intravitreal injections were not toxic to the retina. Our results suggest that a sunitinib preparation with solid lipid nanoparticles for controlled release may offer a significant therapeutic approach for vasoproliferative ocular disease.

Comparison of the original Amsler grid with the preferential hyperacuity perimeter for detecting choroidal neovascularization in age-related macular degeneration.

PURPOSE: To compare the preferential hyperacuity perimeter (Preview PHP; Carl Zeiss Meditec, Dublin, CA) with the original Amsler grid in the detection of choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD). METHODS: Patients were classified into groups, based on the severity of the age-related macular degeneration and underwent preferential hyperacuity perimeter and Amsler grid testing. High sensitivity and or high specificity of a method were defined as the observation of at least 80% of each one the parameters. RESULTS: Sixty-five patients (65 eyes) were analyzed statistically. The sensitivity of detection of choroidal neovascularization was 70% by the Amsler grid and 90% by the preferential hyperacuity perimeter and the specificity of the Amsler grid was 85.5% and that of the preferential hyperacuity perimeter 81.8%. CONCLUSIONS: The preferential hyperacuity perimeter has greater sensitivity than the Amsler grid in the detection of choroidal neovascularization among patients over 50 years of age and is a promising method for monitoring patients with age-related macular degeneration. Although the original Amsler grid is less sensitive, it is a portable method, not expensive, accessible and presents reasonable sensitivity and high specificity in the diagnosis of choroidal neovascularization. Its use can be recommended for self-monitoring in patients with age-related macular degeneration as an alternative to preferential hyperacuity perimeter and when this method is not available.

[Butterfly-shaped pattern dystrophy: case report]. / Distrofia em forma-de-borboleta: relato de caso.

The authors present a case of butterfly-shaped pattern dystrophy diagnosed in a male patient, with retinal pigmented epithelium atrophy and central visual acuity decrease in one of the eyes. The evolution of this case was not benign as described in previous reports. A well-defined lesion located in the posterior pole of both eyes associated with fluorescein angiography allowed the diagnosis of this pattern dystrophy. Optical coherence tomography was performed, showing the aspects of the pathology, for the first time.

Diabetic retinopathy and OCT angiography: clinical findings and future perspectives.

In diabetic retinopathy (DR), macular involvement can present as either macular edema or ischemia. Fluorescein angiography remains the gold standard in the evaluation of retinal vascular perfusion and diagnosis of macular ischemia. However, it is a costly, time-consuming technique, it requires venipuncture, and reports of anaphylaxis and death related to fluorescein injections have been documented, despite their rarity. Optical coherence tomography (OCT) provides a fast and non-invasive method to assess retinal structures at a microscopic level. OCT angiography permits the noninvasive study of retinal and choroid circulation via motion contrast imaging. Split-spectrum amplitude decorrelation angiography combined with OCT angiography has furthered the understanding of retinal and choroidal vascular diseases, allowing the evaluation of retinal microvasculature and identification of subsequent disorders, including DR. Previous studies using OCT angiography have demonstrated that it may demonstrate DR findings such as microaneurysms, arteriolar wall staining, retinal neovascularization, and intraretinal microvascular abnormalities. The purpose of this article is to describe and discuss different concepts regarding OCT angiography, as well as its role in the diagnosis of DR and maculopathy.

Benign familial fleck retina: multimodal imaging including optical coherence tomography angiography.

This report presents multimodal imaging of a 27-year-old woman diagnosed with benign familial fleck retina (OMIM 228980), an uncommon disorder. Fundus photographs revealed retinal flecks that affected her post-equatorial retina but spared the macular area. Fundus autofluorescence and infrared imaging demonstrated a symmetrical pattern of yellow-white fleck lesions that affected both eyes. Her full-field electroretinogram and electrooculogram were normal. An optical coherence tomography B-scan was performed for both eyes, revealing increased thickness of the retinal pigmented epithelium leading to multiple small pigmented epithelium detachments. The outer retina remained intact in both eyes. Spectral-domain optical coherence tomography angiography with split-spectrum amplitude decorrelation algorithm and 3 × 3 mm structural en face optical coherence tomography did not show macular lesions. Benign familial fleck retina belongs to a heterogenous group of so-called flecked retina syndromes, and should be considered in patients with yellowish-white retinal lesions without involvement of the macula.

Multimodal imaging in a patient with combined hamartoma of the retina and retina pigment epithelium / Imagem multimodal em paciente com hamartoma combinado da retina e epitélio pigmentar da retina

ABSTRACT Combined hamartoma of the retina and retinal pigment epithelium is a rare, benign intraocular tumor. Hamartoma of the retina and retinal pigment epithelium has been described in the literature as a condition presenting with variable retinal damage, ranging from partial epiretinal involvement to complete distortion of the retinal layers and retinal pigment epithelium. We report the case of an 8-year-old girl presenting with longstanding strabismus who was diagnosed with Hamartoma of the retina and retinal pigment epithelium based on multimodal imaging assessment. We explored the particular imaging findings from studies using spectral-domain optical coherence tomography, fundus autofluorescence, optical coherence tomography angiography, and fluorescein angiography.

RESUMO O hamartoma combinado de retina e epitélio pigmentar da retina consiste em um tumor intraocular raro com comportamento benigno. O hamartoma combinado de retina e epitélio pigmentar da retina foi descrito na literatura apresentando dano retiniano variável, desde o envolvimento epirretiniano parcial até distorção completa das camadas retinianas e do epitélio pigmentar da retina. Relatamos o caso de uma menina de 8 anos com estrabismo de longa data que foi diagnosticada com hamartoma combinado de retina e epitélio pigmentar da retina, com base na avaliação de imagem multimodal. Exploramos os achados de imagem específicos de estudos usando tomografia de coerência óptica de domínio espectral, autofluorescência, angiografia por tomografia de coerência óptica e angiografia fluorescente.

Pars plana vitrectomy and visual stimulation for treatment of vitreomacular traction secondary to toxoplasmosis retinochoroiditis in a 5-year-old child / Vitrectomia via pars plana e estimulação visual para tratamento da tração vitreomacular secundária à retinocoroidite por toxoplasmose em criança de 5 anos

ABSTRACT Objective: A unusual case of ocular toxoplasmosis with significant vitreomacular traction is reported. The patient improved significantly following pars plana vitrectomy combined with visual stimulation and occlusion therapy. Methods: The case of a 5-year-old girl with significant unilateral vision loss associated with vitreous condensation and macular traction is described. Results: Pars plana vitrectomy was carried out for vitreomacular traction release. This was followed by visual stimulation and occlusion therapy. Significant improvement was observed. Conclusion: Despite structural damage, the combination of properly indicated surgery and amblyopia management strategies allowed the achievement of maximum vision goals in this case, suggesting structural damage may be associated with functional amblyopia.

RESUMO Objetivo: Relata-se um caso de apresentação atípica de toxoplasmose ocular, com importante tração vitreomacular. A paciente apresentou melhora significativa após vitrectomia via pars plana, com estimulação visual e oclusão. Métodos: Descreve-se o caso de uma menina de 5 anos, com importante perda de visão unilateral associada à condensação vítrea e à tração macular. Resultados: Foi realizada vitrectomia via pars plana para alívio da tração vitreomacular, seguida de estimulação visual e oclusão. Foi observada melhora significativa. Conclusão: Apesar dos danos estruturais, a combinação de cirurgia bem indicada com estratégias de tratamento da ambliopia permitiu alcançar o máximo do potencial visual nesta paciente, sugerindo que os danos estruturais podem estar associados à ambliopia funcional.

[Retinopathy in a patient with hepatitis C treated with pegylated interferon and ribavirin: case report]. / Retinopatia em paciente portador de hepatite C tratado com interferon peguilado e ribavirina: relato de caso.

Interferon is an immunomodulating cytokine used to treat patients with different diseases, such as hepatitis C chronic infection. Pegylated interferon is a new type of interferon, developed to increase the half-life of the drug. Many side effects have been related to its use, including ocular toxicity and retinopathy. The most reported ocular findings are cotton-wool spots and hemorrhages located at the posterior pole and surrounding optic nerve head. We describe one case of pegylated interferon-associated retinopathy with visual loss. The patient had visual acuity improvement four weeks after discontinuation of the medication and the ocular findings became much more subtle.

Initial experience with ocriplasmin in the treatment of vitreomacular traction.

This study aimed to report the clinical and structural outcomes of intravitreal ocriplasmin in the treatment of vitreomacular interface disorders in two tertiary centers in Brazil. A retrospective study was performed by reviewing medical records and spectral domain optical coherence tomography (SD-OCT) findings of seven patients who were treated with a single ocriplasmin injection. A total of 57.14% of patients achieved resolution of vitreomacular traction as evidenced by SD-OCT. Regarding our functional results, 87.71% maintained or improved visual acuity after follow-up. To the best of our knowledge, this is the first study reporting initial results of ocriplasmin therapy in Brazil.