Image quality comparison of AirDoc portable retina camera versus eyer in a diabetic retinopathy screening program.

BACKGROUND: Diabetic retinopathy (DR) stands as the foremost cause of preventable blindness in adults. Despite efforts to expand DR screening coverage in the Brazilian public healthcare system, challenges persist due to various factors including social, medical, and financial constraints. Our objective was to evaluate the quality of images obtained with the AirDoc, a novel device, compared to Eyer portable camera which has already been clinically validated. METHODS: Images were captured by two portable retinal devices: AirDoc and Eyer. The included patients had their fundus images obtained in a screening program conducted in Blumenau, Santa Catarina. Two retina specialists independently assessed image's quality. A comparison was performed between both devices regarding image quality and the presence of artifacts. RESULTS: The analysis included 129 patients (mean age of 61 years), with 29 (43.28%) male and an average disease duration of 11.1 ± 8 years. In Ardoc, 21 (16.28%) images were classified as poor quality, with 88 (68%) presenting artifacts; in Eyer, 4 (3.1%) images were classified as poor quality, with 94 (72.87%) presenting artifacts. CONCLUSIONS: Although both Eyer and AirDoc devices show potential as screening tools, the AirDoc images displayed higher rates of ungradable and low-quality images, that may directly affect the DR and DME grading. We must acknowledge the limitations of our study, including the relatively small sample size. Therefore, the interpretations of our analyses should be approached with caution, and further investigations with larger patient cohorts are warranted to validate our findings.

Patients Perceptions of Artificial Intelligence in a Deep Learning-Assisted Diabetic Retinopathy Screening Event: A Real-World Assessment.

During an artificial intelligence (AI)-assisted diabetic retinopathy screening event, we performed a survey on patients´ perceptions on AI. Respondents were individuals with diabetes, mostly followed in primary healthcare with a low education level. While 49.6% of participants said they knew what AI was, only 14% reported good or expert knowledge of AI. The vast majority reported positive feelings towards AI in healthcare. We highlight the importance of understanding patients´ views regarding AI in health in a real-life situation and emphasize the importance of digital education.

Review of real-world evidence of dual inhibition of VEGF-A and ANG-2 with faricimab in NAMD and DME.

Management of vitreoretinal disorders (e.g., neovascular age-related macular degeneration [nAMD] and diabetic macular edema [DME]) have assumed the standard therapy of lifelong anti-VEGF injections with drugs like aflibercept, brolucizumab, ranibizumab and bevacizumab. However, the burden imposed on patients is a major deterrent for continual therapy and recovery. Faricimab, a bispecific antibody, blocking both VEGF-A and Ang-2 molecules, produces a comparable functional and anatomical results, with less injections, significantly reducing patient burden. Visual acuity, safety, adverse effects, and anatomical outcomes are discussed in the pivotal clinical trials (YOSEMITE/RHINE and TENAYA/LUCERNE), and early data from real-world studies (TRUCKEE, TAHOE, FARWIDE-DME, FARETINA and others). In YOSEMITE and RHINE, faricimab demonstrated non-inferior vision gains, better anatomical outcomes compared to aflibercept every 8 weeks. Faricimab in the personalized treatment interval (PTI), after week 96, achieved 12-week interval in 78.1% of the patients and 16-week interval in 62.3%. TENAYA and LUCERNE reported comparable best corrected visual acuity (BCVA) improvement and better anatomic outcomes during head-to-head phase, parallel to aflibercept, at its 8-week treatment schedule. Faricimab in the PTI regimen, after week 96 achieved 12-week interval in 77.8% of the patients and 16-week interval in 63.1%. Safety of faricimab has been comparable to aflibercept in these pivotal trials. Real-world data supports the data from the pivotal studies regarding the efficacy and safety profile of faricimab in heterogenous real world patient population. Moreover, in previously treated patients, it also demonstrated a faster fluid resolution, good safety profile. Considering faricimab has demonstrated anatomic and durability benefit in the treatment of nAMD and DME, additional data from ongoing extension clinical trials, AVONELLE-X and RHONE-X will help understand longer term outcomes for patients treated with faricimab as well as patients switching from aflibercept to faricimab after finishing the pivotal trials. Longer term data from the real-world studies will also continue to contribute to our understanding of long-term efficacy, safety and durability in the real world patient population.

Single retinal image for diabetic retinopathy screening: performance of a handheld device with embedded artificial intelligence.

BACKGROUND: Diabetic retinopathy (DR) is a leading cause of blindness. Our objective was to evaluate the performance of an artificial intelligence (AI) system integrated into a handheld smartphone-based retinal camera for DR screening using a single retinal image per eye. METHODS: Images were obtained from individuals with diabetes during a mass screening program for DR in Blumenau, Southern Brazil, conducted by trained operators. Automatic analysis was conducted using an AI system (EyerMaps™, Phelcom Technologies LLC, Boston, USA) with one macula-centered, 45-degree field of view retinal image per eye. The results were compared to the assessment by a retinal specialist, considered as the ground truth, using two images per eye. Patients with ungradable images were excluded from the analysis. RESULTS: A total of 686 individuals (average age 59.2 ± 13.3 years, 56.7% women, diabetes duration 12.1 ± 9.4 years) were included in the analysis. The rates of insulin use, daily glycemic monitoring, and systemic hypertension treatment were 68.4%, 70.2%, and 70.2%, respectively. Although 97.3% of patients were aware of the risk of blindness associated with diabetes, more than half of them underwent their first retinal examination during the event. The majority (82.5%) relied exclusively on the public health system. Approximately 43.4% of individuals were either illiterate or had not completed elementary school. DR classification based on the ground truth was as follows: absent or nonproliferative mild DR 86.9%, more than mild (mtm) DR 13.1%. The AI system achieved sensitivity, specificity, positive predictive value, and negative predictive value percentages (95% CI) for mtmDR as follows: 93.6% (87.8-97.2), 71.7% (67.8-75.4), 42.7% (39.3-46.2), and 98.0% (96.2-98.9), respectively. The area under the ROC curve was 86.4%. CONCLUSION: The portable retinal camera combined with AI demonstrated high sensitivity for DR screening using only one image per eye, offering a simpler protocol compared to the traditional approach of two images per eye. Simplifying the DR screening process could enhance adherence rates and overall program coverage.

TRANSPLANTATION OF SUBRETINAL STEM CELL-DERIVED RETINAL PIGMENT EPITHELIUM FOR STARGARDT DISEASE: A Phase I Clinical Trial.

PURPOSE: To assess the safety of injecting human embryonic stem cell retinal pigment epithelial cell dose to treat Stargardt disease. METHODS: In this prospective, Phase I clinical trial, human embryonic stem cell retinal pigment epithelial cells in suspension were injected into the subretinal space in eyes with the worse best-corrected visual acuity (BCVA). After vitrectomy/posterior hyaloid removal, a partial retinal detachment was created and the human embryonic stem cell retinal pigment epithelial cells were administered. Phacoemulsification with intraocular lens implantation was performed in eyes with lens opacity. All procedures were optical coherence tomography-guided. The 12-month follow-up included retinal imaging, optical coherence tomography, visual field/electrophysiologic testing, and systemic evaluation. The main outcome was the absence of ocular/systemic inflammation or rejection, tumor formation, or toxicity during follow-up. RESULTS: The mean baseline BCVAs in the phacoemulsification and no phacoemulsification groups were similar (1.950 ± 0.446 and 1.575 ± 0.303, respectively). One year postoperatively, treated eyes showed a nonsignificant increase in BCVA. No adverse effects occurred during follow-up. Intraoperative optical coherence tomography was important for guiding all procedures. CONCLUSION: This surgical procedure was feasible and safe without cellular migration, rejection, inflammation, or development of ocular or systemic tumors during follow-up.

Spectral domain oct for screening of macular diseases prior to multifocal intraocular lens implantation.

BACKGROUND: Cataract surgery with multifocal IOLs could give patients good vision and great satisfaction, at the same time generating high expectations; therefore, its precise indication is essential if we are to reach our goal. The use of optical coherence tomography may be a valuable tool in the screening of macular diseases, which often cannot be detected in routine clinical examinations. This study evaluates the benefit of including spectral domain optical coherence tomography (SD-OCT) in routine preoperative cataract surgery protocols for better case selection in multifocal IOLs. METHODS: Observational and retrospective clinical study that includes patients with an indication for multifocal IOL implantation who underwent retinal fundus exam and SD-OCT examination between 2018 and 2019. The clinical examination with ophthalmoscopy and SD-OCT imaging results were evaluated to observe their influence on the final choice of the lens implanted lens in cataract surgery. RESULTS: 405 eyes from 207 patients with multifocal IOL indication were included. It was found that 220 (54.2%) of all indicated multifocal or trifocal IOLs were in fact implanted. The most important reason for not implanting the indicated IOL was financial, in 116 (59.46%) eyes. The second cause were retinal abnormalities detected by SD-OCT, 63 eyes (15.6%). Those abnormalities included dry age-related macular degeneration (AMD) (50.7%), neovascular AMD (3.1%), vitreomacular adhesion (11.1%), diabetic macular edema (3.1%), epiretinal membrane (ERM) (25.3%) and other macular abnormalities (6.3%). Of the 63 eyes with an abnormal SD-OCT result, 44 (69.8%) were also identified by fundus examination. Nineteen (30.2%) eyes had abnormalities detected only by SD-OCT imaging with a normal clinical exam. CONCLUSIONS: Routine use of SD-OCT imaging may help diagnose pre-existing macular pathologies not identified by clinical exam, helping both physicians and patients choose the ideal IOL individually and has the potential to prevent unsatisfactory functional results.

Retinal vascular occlusion in patients with the Covid-19 virus.

BACKGROUND: The coronavirus disease (COVID-19) can cause acute respiratory distress syndrome with dyspnea, anosmia, fever, and cough. Few studies describing ocular findings have been reported. The current case series, reports the clinical findings and natural history of patients with retinal vascular occlusion after COVID-19 infection. CASE PRESENTATIONS: Patients from multiple Brazilian hospitals who had clinical and laboratory diagnoses of COVID-19 with retinal vein or arterial occlusion were analyzed retrospectively. The baseline demographics, clinical presentations of COVID-19, comorbidities, risk factors for thromboembolic events, and use of anticoagulant drugs were reviewed. The relevant clinical findings associated with the retinal vascular occlusive event, management, and outcomes were reported. Fourteen cases of retinal vascular occlusion within 3 months of the laboratory confirmed COVID-19 infection were identified. Three of which required hospitalization for COVID-19 management. Eight cases had central retinal vein occlusion, three branch retinal vein occlusion, one hemispheric retinal vein occlusion, and two central arterial occlusion. The mean patient age at presentation was 48 years; the visual acuity ranged from light perception to 20/20. Nine patients received intravitreal injections of anti-angiogenic drugs and one received ketorolac tromethamine drops for the management of secondary macular edema; four were untreated. CONCLUSIONS: COVID-19 patients may rarely have ocular manifestations of the disease. It was presented a case series of vascular occlusion events that may be related to COVID-19 infection, since these thrombotic events are actively involved in the disease pathophysiology. These cases emphasize the need for further investigation of ocular complications associated with this disease.

Effects of phosphodiesterase type 5 inhibitors on choroid and ocular vasculature: a literature review.

To provide information on the effects of phosphodiesterase type 5 (PDE5) inhibitors on choroidal vessels and central serous chorioretinopathy (CSC) and possible implications for development of exudative age-related macular degeneration (AMD). Two independent investigators conducted a qualitative review of PubMed to identify studies on the choroidal effect of PDE5 inhibitors in June 2019. The search used key words that included PDE5 inhibitors, sildenafil, tadalafil, vardenafil, choroid, choroidal flow, choroidal vessels, choroidal thickness, CSC, AMD or a combination. Only studies which assessed choroidal findings were included. Many ocular diseases are related to changes in choroidal thickness and perfusion. Patients with AMD, who have decreased choroidal perfusion, may manifest more severely diminished choroidal ability to deliver oxygen and other metabolites to the retina, leading to growth of neovascular tissue. As a result of this engorgement of the choroidal vasculature, some patients may have leakage across the retinal pigment epithelium (RPE) and accumulation of subretinal fluid, resulting in CSC. Transient visual symptoms, i.e., changes in color perception and increased light sensitivity, are well-known adverse effects, but there have been rare reports of vision-threatening ocular complications in users of PDE5 inhibitors, such as nonarteritic anterior ischemic optic neuropathy and cilioretinal artery occlusion. The choroid is a vascular tissue analogous in many respects to the corpus cavernosum, and PDE5 inhibitors may increase the choroidal thickness and perfusion. While it is intuitively obvious that thickness of the choroid alone does not guarantee better choriocapillaris oxygenation, it is a reasonable step towards ameliorating ischemia. These drugs have numerous physiologic effects on the choroid related to blood flow, such as clinical consequences in CSC and AMD.

Association between ocular abnormalities and systemic diseases in Down Syndrome patients / Associação entre achados oftalmológicos e comorbidades em pacientes com Síndrome de Down

Abstract Objectives: Describe ocular findings and its correlation with systemic diseases in Down Syndrome (DS) pediatric patients. Methods: Quantitative and cross-sectional study of prevalence with children aged from 0 to 25 years. Standard ophthalmic examinations performed: visual acuity, slit lamp biomicroscopy, ocular motility, static refraction and indirect ophthalmoscopy. Ocular findings were associated with comorbidities available in pediatric records of patients in FURB Down Syndrome Outpatient clinic, in which they have regular follow-up. Results: A total of 76 patients were evaluated (33 males and 43 females). Of these, 72 patients (94.73%) had ocular abnormalities. Refractive errors were the most prevalent (94.73%), followed by alterations in indirect ophthalmoscopy (40.8%), biomicroscopy (15.8%), ocular motility (15.8%) and epiphora (9.2%). From the refractive changes 13.15% had myopia; 76.31% had hypermetropia and 47.36% had astigmatism. Sytemic abnormalities were observed in 73 children. The most prevalent was thyroid diseases presented in 65.79%, followed by heart disease 61.84%, gastrointestinal disease (15.79%); abdominal hernias (14.4%); respiratory changes (14.4%); genitourinary alterations (10.53%); musculoskeletal alterations (10.53%) and epilepsy (3.95%). There was statically significant association between the presence of myopia and hypothyroidism (p = 0.01); astigmatism and heart diseases (p = 0.003); and astigmatism and genitourinary alterations (p = 0.001). Conclusion: There was a high prevalence of ophthalmologic abnormalities in this study of children with Down Syndrome. Associations between myopia and hypothyroidism, astigmatism and heart diseases, and astigmatism and genitourinary disorders were found. More studies and increase of the sample are necessary to confirm the associations of ophthalmologic abnormalities with most common systemic diseases in this population.

Resumo Objetivos: Descrever as alterações oculares e sua correlação com outras comorbidades em pacientes pediátricos com Síndrome de Down (SD). Métodos: Estudo quantitativo de prevalência com delineamento transversal em crianças de 0 a 25 anos portadoras de SD. Realizados exames oftalmológicos de acuidade visual, biomicroscopia anterior, motilidade ocular, refração estática objetiva ou subjetiva conforme o nível de cooperação do paciente e oftalmoscopia indireta. Os achados foram correlacionados com as comorbidades disponíveis nos prontuários dos pacientes do Ambulatório de Síndrome de Down da FURB, no qual são acompanhados regularmente. Resultados: Foram avaliados 76 pacientes (33 do sexo masculino e 43 do sexo feminino). Dentre esses, 72 pacientes (94,73%) tiveram alterações oculares. Alterações refrativas foram as mais prevalentes (94,73%), seguidas de alterações na oftalmoscopia indireta (40,8%), biomicroscopia (15,8%), motilidade ocular (15,8%) e epífora (9,2%). Das alterações refrativas 13,15% tiveram miopia; 76,31% tiveram hipermetropia e 47,36% tiveram astigmatismo. Na amostra, 73 pacientes possuíam alguma comorbidade. A mais prevalente foi a alteração de tireoide, presente em 65,79% dos pacientes, seguido de alterações cardíacas (61,84%), alterações gastrointestinais (15,79%), hérnias abdominais (14,4%), alterações respiratórias (14,4%), alterações geniturinárias (10,53%), alterações osteomusculares (10,53%) e epilepsia (3,95%). Houve associações significativas entre miopia e hipotireoidismo (p = 0,01); astigmatismo e cardiopatias (p = 0,003); e astigmatismo e alterações geniturinárias (p = 0,001). Conclusão: Houve alta prevalência de alterações oftalmológicas na amostra. Foram encontradas associações entre miopia e hipotireoidismo, astigmatismo e cardiopatias, e astigmatismo e alterações geniturinárias. Mais estudos e aumento da amostra são necessários para confirmar os resultados das associações nessa população.

Development of a new tissue injector for subretinal transplantation of human embryonic stem cell derived retinal pigmented epithelium.

BACKGROUND: Subretinal cell transplantation is a challenging surgical maneuver. This paper describes the preliminary findings of a new tissue injector for subretinal implantation of an ultrathin non-absorbable substrate seeded with human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE). METHODS: Ultrathin Parylene-C substrates measuring 3.5 mm × 6.0 mm seeded with hESC-RPE (implant referred to as CPCB-RPE1) were implanted into the subretinal space of 12 Yucatan minipigs. Animals were euthanized immediately after the procedure and underwent spectral domain optical coherence tomography (SD-OCT) and histological analysis to assess the subretinal placement of the implant. Evaluation of the hESC-RPE cells seeded on the substrate was carried out before and after implantation using standard cell counting techniques. RESULTS: The tissue injector delivered the CPCB-RPE1 implant through a 1.5 mm sclerotomy and a 1.0-1.5 mm retinectomy. SD-OCT scans and histological examination revealed that substrates were precisely placed in the subretinal space, and that the hESC-RPE cell monolayer continued to cover the surface of the substrate after the surgical procedure. CONCLUSION: This innovative tissue injector was able to efficiently deliver the implant in the subretinal space of Yucatan minipigs, preventing significant hESC-RPE cell loss, minimizing tissue trauma, surgical complications and postoperative inflammation.

The Use of Vital Dyes during Vitreoretinal Surgery - Chromovitrectomy.

The aim of this article is to present the current data with regard to the application of vital dyes during vitreoretinal surgery, 'chromovitrectomy', as well as to overview the current literature regarding the properties of dyes, techniques of application, indications and complications in chromovitrectomy. It is well known that indocyanine green is toxic to the retina and consequently not the ideal dye for chromovitrectomy. Different vital dyes has been tested for chromovitrectomy including trypan blue, patent blue, triamcinolone acetonide, infracyanine green, sodium fluorescein and brilliant blue. Brilliant blue seems to be the ideal dye for internal limiting membrane due to its afinity, lower toxic profile and to reduce the appearance of apoptosis. Besides the dye itself, the injection technique is crucial to avoid additional toxicity, slow injection, far from the retina and protection of the macular hole are some tips. More recently the use of dyes has been applied to stain perfluorcarbon liquids that may enhance its visualization during vitrectomy.

Association Between Growth of Geographic Atrophy and the Complement Factor I Locus.

The association between the growth of geographic atrophy (GA) and a single nucleotide polymorphism (SNP) in the complement factor I (CFI) locus was investigated in the COMPLETE trial. Growth of GA at 52 weeks in eyes without the CFI at-risk allele was slightly faster than the growth in eyes with the CFI at-risk allele (P ≥ .72). The authors of the current study found that in contrast to the faster growth rate reported in CFI-positive eyes from the MAHALO trial, the CFI positive eyes in the COMPLETE trial did not grow faster, and this analysis included 24 eyes that met the MAHALO eligibility criteria.

Comparison of Geographic Atrophy Growth Rates Using Different Imaging Modalities in the COMPLETE Study.

BACKGROUND AND OBJECTIVE: To compare the measurements and growth rates of geographic atrophy (GA) secondary to age-related macular degeneration (AMD) obtained using different imaging modalities. PATIENTS AND METHODS: Thirty patients with AMD and GA measuring from 1.25 mm² to 18 mm² based on spectral-domain optical coherence tomography (SD-OCT) fundus imaging were enrolled. Imaging was performed at baseline and at follow-up months 3, 6, 9, and 12, including autofluorescence (AF) imaging with a fundus camera-based flash system (TRC-50DX; Topcon Medical Systems, Oakland, NJ; AF excitation λ: 535-585 nm; detection λ: 605-715 nm), AF and fluorescein angiography (FA) imaging with a confocal scanning laser ophthalmoscopy (SLO) system (Spectralis; Heidelberg Engineering, Heidelberg, Germany; AF excitation λ: 488 nm; detection λ: > 500 nm), and SD-OCT en face imaging (Cirrus; Carl Zeiss Meditec, Dublin, CA). RESULTS: Average baseline square root measurements and enlargement rates of square root areas appeared similar across all modalities; 0.2 mm was the largest difference between any pair of measurement means. The intraclass correlation coefficients (ICC) were essentially equal to 1 for all comparisons of area measurements but were lower for growth rates than area measurements. Comparison of 26-week average enlargement rates showed no significant difference between the SLO AF image and enhanced SD-OCT en face image (mean difference: 0.01 mm; SD: 0.10; P = .70). CONCLUSION: Agreement among all imaging modalities in measuring the areas of GA at baseline diminished when the growth rates of GA were compared over 26 weeks, likely because each imaging technique identifies different anatomic features along the border of GA, which may appear similar but change at different rates.

Diabetes induces changes in neuroretina before retinal vessels: a spectral-domain optical coherence tomography study.

PURPOSE: To investigate retinal changes prior to vascular signs in patients with type 2 diabetes without diabetic retinopathy or with mild non proliferative diabetic retinopathy. METHODS: A cross-sectional study was performed in three groups: patients without diabetes, patients with type 2 diabetes without diabetic retinopathy, and patients with diabetes with mild diabetic retinopathy. Analysis of retinal layers was performed objectively with the Cirrus Review Software 6.0 (Carl Zeiss Meditec, Dublin, CA, USA). Macular cube scans were analyzed with regard to: the ganglion cell layer + inner plexiform layer analysis, retinal nerve fiber layer thickness, central subfoveal retinal thickness and average macular thickness. RESULTS: In total, 102 patients were included in this study, of which 28 (27.4%) were classified into control group, 46 (45.0%) classified as diabetic patients with no diabetic retinopathy and 28 (27.4%) classified as mild diabetic retinopathy. Quantitative analysis with the Cirrus software showed that the mean ganglion cell layer and mean retinal nerve fiber layer were thinner in diabetes without diabetic retinopathy group when compared to controls. ANOVA with Bonferroni post test indicated a statistically significant reduction in average retinal thickness in mild diabetic retinopathy group (P = 0.032) compared to control and reduction in ganglion cell layer in diabetes with no diabetic retinopathy (P = 0.039) and mild diabetic retinopathy (P = 0.003). Also indicated reduction in retinal nerve fiber layer in diabetic without diabetic retinopathy and eyes with mild diabetic retinopathy (P < 0.001), compared to controls. CONCLUSIONS: Our study found reduction in thickness of ganglion cell layer and retinal nerve fiber layer in patients with diabetes without diabetic retinopathy, which suggests neuroretinal changes before vascular signs of diabetic retinopathy.

Preclinical investigations of intravitreal ziv-aflibercept.

BACKGROUND AND OBJECTIVE: To investigate the retinal safety of intravitreal (IVT) ziv-aflibercept in rabbits. MATERIALS AND METHODS: Eighteen rabbits were given an IVT injection of ziv-aflibercept (25 mg/mL) or aflibercept (40 mg/mL) and examined by funduscopy, electroretinography (ERG), optical coherence tomography (OCT), light microscopy, and transmission electron microscopy (TEM). Serum, aqueous, and vitreous were obtained afterward for osmolarity analysis. The effect of ziv-aflibercept on human retinal cultured cells (ARPE-19) was assessed by the MTT cell viability assay. RESULTS: All eyes showed normal funduscopy, OCT, and ERG findings at baseline and 24 hours or 7 days after the procedure. Median baseline serum, vitreous, and aqueous osmolarity remained unchanged. Histology and TEM showed no major anatomic signs of toxicity. No cytotoxic effect was observed in ARPE-19 cells exposed to ziv-aflibercept. CONCLUSION: IVT injection ziv-aflibercept at a concentration of 25 mg/mL proved to be safe for the rabbit retina.

Retinal biocompatibility of brilliant blue g with deuterated water for chromovitrectomy.

PURPOSE: To investigate the retinal biocompatibility of Brilliant Blue G with deuterated water (BBG-D2O) as a vital dye for chromovitrectomy. METHODS: In this animal study, 0.05 mL of 0.25 g/L Brilliant Blue G (BBG) associated with 0.13 mL/mL of deuterium oxide (D2O) was injected intravitreally in the right eye and the same amount of balanced salt solution (BSS) was injected similarly in the left eye of rabbits. Clinical examination and histology with light microscopy were performed after seven days. Retinal cell layers were evaluated for morphologic alterations. Electroretinographic (ERG) changes were also assessed at baseline and 7 days after the injections. RESULTS: A total of 6 rabbits were included in the study. The gross histopathologic appearance of the retina, choroid, sclera and optic nerve was within normal limits without any sign of severe retinal necrosis or cystic degeneration. Light microscopy showed that BBG-D2O caused no substantial alterations in retinal layers as compared to control eyes. The injection of BBG-D2O did not induce considerable functional ERG alterations. CONCLUSION: Intravitreal injection of BBG-D2O 0.25 g/L seems to induce no retinal toxicity as documented by lack of functional and histological changes.

Safety and efficacy of various concentrations of topical lidocaine gel for intravitreal injection.

INTRODUCTION: Intravitreal injection (IVT) is one of the most common vitreoretinal procedures, a large majority are performed with local anesthesia. The purpose of this study was to investigate the safety to the cornea and anesthetic efficacy of five concentrations of lidocaine gel. METHODS: A prospective clinical trial was conducted testing lidocaine gel in five preparations: 2, 3.5, 5, 8 and 12%. Patients with macular degeneration, diabetic edema or retina vein occlusion were scheduled for intravitreal treatment received topical anesthesia with lidocaine gel 5 and 10 min before the procedure. Patients answered the visual analog scale for pain during the procedure. Corneal and conjunctival was evaluated using the Oxford scale. RESULTS: In total, 260 patients were randomized into five groups. The mean pain scores (± standard deviation) were 2.63 (± 1.68) in the 2% group, 2.08 (± 1.35) in the 3.5%; 2.00 (± 1.65) in the 5%, 1.93 (± 1.40) in the 8% and 1.83 (± 1.35) in the 12% group. Mean pain score among all groups was similar (p = 0.077). There was no significant difference between groups in regard to keratitis mean score (p = 0.897). CONCLUSIONS: Lidocaine gel at concentrations from 2 to 12% induced similar anesthetic effect for IVTs, without adverse effects on cornea and conjunctiva.

Development and initial experience with a colored perfluorocarbon liquid for intraocular tamponade in vitreoretinal surgery.

PURPOSE: To present the development and initial experience of a novel colored perfluorocarbon liquid (PFCL) in vitreoretinal surgery. METHODS: This was an experimental laboratory study and prospective human interventional study. F6H8 (Fluoron GmbH) was colored by adding 0.3 g/L blue anthraquinone dye. Subsequently, 20% colored F6H8 was prepared by mixing with perfluorooctane or perfluorodecalin (Fluoron GmbH). The novel product is not yet FDA approved for human application. In the laboratory, the colored PFCL was covered with 1) uncolored PFCL, 2) BSS, and 3) silicone oil. Cell toxicity was evaluated in L929 mouse fibroblasts using a growth inhibition assay. Porcine ex vivo eyes were evaluated after vitrectomy followed by intravitreal and subretinal colored PFCL infusion. A pilot, prospective, noncomparative interventional study was conducted in patients with retinal detachment with proliferative vitreoretinopathy (PVR). RESULTS: The density of the colored PFLC mixture was 1.664 g/cm for perfluorooctane and 1.802 g/cm for perfluorodecalin. There was no relevant cell growth inhibition with any concentration of colored PFCL tested. Experiments in pigs revealed that infusion of the colored PFCL caused neither staining of the internal limiting membrane nor intravitreal residual droplets. In the prospective study, 9 eyes (75%) underwent surgery for rhegmatogenous retinal detachment with at least grade C PVR. The colored PFCL enabled retinal break examination and detection of residual intravitreal droplets in all surgeries. There was no case of separation or leakage of the dye from the PFCL solution that could have caused unwanted staining of the vitreous or epiretinal surface. CONCLUSION: The colored PFCL enabled intraoperative maneuvers such as endolaser use. In addition, removal of the colored PFCL was easily achieved at the end of surgery.

Vital dyes in ophthalmology: a chemical perspective.

Vital dyes have advanced diagnosis and surgical technique in various specialties, including oncology, gastroenterology and ophthalmology. Intra-operative and diagnostic dyes are finding uses in all areas of ophthalmology, including cornea, cataract, retina, glaucoma, orbit and conjunctiva. We provide a summary of current knowledge of the chemical concepts of vital dyes in ophthalmology. We review the properties of dyes, techniques of application, indications and complications in ocular surgery. Vital dyes represent an expanding area of research, and novel dyes deserve further investigation.

Change in drusen volume as a novel clinical trial endpoint for the study of complement inhibition in age-related macular degeneration.

BACKGROUND AND OBJECTIVE: To evaluate the change in drusen volume following treatment with eculizumab, a systemic inhibitor of complement component 5. PATIENTS AND METHODS: Single-center, prospective, randomized, double-masked clinical trial. Patients were randomized 2:1 to receive intravenous eculizumab or placebo over 26 weeks. MAIN OUTCOME MEASURE: decrease in drusen volume of at least 50% at 26-week follow-up. RESULTS: Mean drusen cube root volumes were 0.49 mm and 0.47 mm (P = .64) at baseline and 0.51 mm and 0.42 mm (P = .17) at 26 weeks in the eculizumab and placebo groups, respectively. In the placebo group, one eye had a decrease in drusen volume of at least 50% and two eyes developed neovascularization through 26 weeks. CONCLUSION: Systemic complement inhibition with eculizumab did not significantly reduce drusen volume. Drusen growth was dependent on the number of complement at-risk alleles. Future trials should consider the use of a composite clinical trial endpoint in which efficacy is defined by the treatment's ability to prevent drusen growth, neovascularization, and the formation of geographic atrophy over 1 year.