First-in-Human Robot-Assisted Subretinal Drug Delivery Under Local Anesthesia.

PURPOSE: To report the results of a first-in-human study using a robotic device to assist subretinal drug delivery in patients undergoing vitreoretinal surgery for macular hemorrhage. DESIGN: Double-armed, randomized controlled surgical trial (ClinicalTrials.gov identifier: NCT03052881). METHODS: The study was performed at the Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom. In total, 12 participants were recruited-6 in the robot-assisted and 6 in the control manual surgery arm according to the prespecified inclusion and exclusion criteria. All subjects presented with acute loss of vision owing to a subfoveal hemorrhage secondary to neovascular age-related macular degeneration. After standard vitrectomy, intraoperative optical coherence tomography-guided subretinal injection of tissue plasminogen activator (TPA) was performed by either robot-assisted or conventional manual technique under local anesthesia. The robotic part of the procedure involved advancement of a cannula through the retina and stabilizing it during foot-controlled injection of up to 100 µL of TPA solution. We assessed surgical success, duration of surgery, adverse events, and tolerability of surgery under local anesthesia. RESULTS: The procedure was well tolerated by all participants and safely performed in all cases. Total duration of surgery, time taken to complete the injection, and retinal microtrauma were similar between the groups and not clinically significant. Subretinal hemorrhage was successfully displaced at 1 month postintervention, except for 1 control subject, and the median gain in visual acuity was similar in both arms. CONCLUSIONS: This first-in-human study demonstrates the feasibility and safety of high-precision robot-assisted subretinal drug delivery as part of the surgical management of submacular hemorrhage, simulating its potential future application in gene or cell therapy.

Using optical coherence tomography angiography to guide the treatment of pathological myopic patients with submacular hemorrhage.

The present study aimed to investigate whether optical coherence tomography angiography (OCTA) could be used to guide the treatment of pathological myopic patients with submacular hemorrhage. Two pathological myopia patients with submacular hemorrhage were examined. Initially, choroidal neovascularization (CNV) was not observed during fundus angiography in both patients. However, based on OCTA, the first patient was diagnosed with myopic lacquer crack-related macular hemorrhage, and the second with CNV secondary to punctate inner choroidopathy. The first patient was treated with traditional Chinese medicine administered orally, and the second with intravitreal injections of anti-vascular endothelial growth factor (VEGF). Lesions in both patients were resolved. Submacular hemorrhage in pathological myopia patients could be caused by numerous mechanisms. OCTA is useful in differentiating inflammatory CNV from inflammatory lesions, particularly if CNV is not detected using other multimodal imaging techniques.

A Deep Phenotype Association Study Reveals Specific Phenotype Associations with Genetic Variants in Age-related Macular Degeneration: Age-Related Eye Disease Study 2 (AREDS2) Report No. 14.

PURPOSE: Age-related macular degeneration (AMD), a multifactorial disease with variable phenotypic presentation, was associated with 52 single nucleotide polymorphisms (SNPs) at 34 loci in a genome-wide association study (GWAS). These genetic variants could modulate different biological pathways involved in AMD, contributing to phenotypic variability. To better understand the effects of these SNPs, we performed a deep phenotype association study (DeePAS) in the Age-Related Eye Disease Study 2 (AREDS2), followed by replication using AREDS participants, to identify genotype associations with AMD and non-AMD ocular and systemic phenotypes. DESIGN: Cohort study. PARTICIPANTS: AREDS and AREDS2 participants. METHODS: AREDS2 participants (discovery cohort) had detailed phenotyping for AMD; other eye conditions; cardiovascular, neurologic, gastrointestinal, and endocrine disease; cognitive function; serum nutrient levels; and others (total of 139 AMD and non-AMD phenotypes). Genotypes of the 52 GWAS SNPs were obtained. The DeePAS was performed by correlating the 52 SNPs to all phenotypes using logistic and linear regression models. Associations that reached Bonferroni-corrected statistical significance were replicated in AREDS. MAIN OUTCOME MEASURES: Genotype-phenotype associations. RESULTS: A total of 1776 AREDS2 participants had 5 years follow-up; 1435 AREDS participants had 10 years. The DeePAS revealed a significant association of the rs3750846 SNP at the ARMS2/HTRA1 locus with subretinal/sub-retinal pigment epithelial (RPE) hemorrhage related to neovascular AMD (odds ratio 1.55 [95% confidence interval 1.31-1.84], P = 2.67 × 10-7). This novel association remained significant after conditioning on participants with neovascular AMD (P = 2.42 × 10-4). Carriers of rs3750846 had poorer visual acuity during follow-up (P = 6.82 × 10-7) and were more likely to have a first-degree relative with AMD (P = 5.38 × 10-6). Two SNPs at the CFH locus, rs10922109 and rs570618, were associated with the drusen area in the Early Treatment Diabetic Retinopathy Study Report (ETDRS) grid (P = 2.29 × 10-11 and P = 3.20 × 10-9, respectively) and the center subfield (P = 1.24 × 10-9 and P = 6.68 × 10-8, respectively). SNP rs570618 was additionally associated with the presence of calcified drusen (P = 5.38 × 10-6). Except for positive family history of AMD with rs3750846, all genotype-phenotype associations were significantly replicated in AREDS. No pleiotropic associations were identified. CONCLUSIONS: The association of the SNP at the ARMS2/HTRA1 locus with subretinal/sub-RPE hemorrhage and poorer visual acuity and of SNPs at the CFH locus with drusen area may provide new insights in pathophysiological pathways underlying different stages of AMD.

Primera manifestación oftalmológica de una sepsis por Klebsiella. Importancia de la sospecha diagnóstica precoz / Endogenous endophthalmitis as a first clinical manifestation of Klebsiella sepsis. The importance of an early diagnosis

Caso clínico: Paciente diabético que desarrolla una uveítis unilateral con un foco de coriorretinitis en el ojo derecho asociada a fiebre y disminución de la visión. Sospechándose una endoftalmitis endógena se realizaron pruebas complementarias encontrándose abscesos hepáticos con biopsia positiva para Klebsiella. La afectación ocular se fue resolviendo gracias a antibioticoterapia intravenosa y al drenaje percutáneo de los abscesos. Conclusión: La endoftalmitis endógena por Klebsiella es un hallazgo poco frecuente con consecuencias graves. Un diagnóstico y un tratamiento antibioticoterápico tempranos pueden mejorar el cuadro aunque la visión resultante suele ser pobre(AU)

Case report: A diabetic patient who developed a unilateral uveitis with a chorioretinitis patch in his right eye associated with decreased visual acuity and fever. Endogenous endophthalmitis was suspected and complementary tests were performed, finding hepatic abscesses with Klebsiella isolation in the biopsy. The ocular disorder slowly improved with intravenous therapy and guided percutaneous liver drainage. Conclusion: Endogenous Klebsiella endophthalmitis is an uncommon condition with severe complications. An early diagnosis and aggressive antibiotic therapy can ameliorate the final course but the visual outcome still remains poor(AU)

A review of the French maritime pine bark extract (Pycnogenol), a herbal medication with a diverse clinical pharmacology.

OBJECTIVES: An increasing body of evidence indicates that Pycnogenol (PYC), a standardized extract of French maritime pine bark, has favorable pharmacological properties. This is a review of studies with both PYC and components of the preparation, that have helped to elucidate target sites and possible mechanisms for activity in men. METHODS: Studies appearing in peer reviewed literature, as well as results presented at international meetings not yet available as published papers, are included in this review. Additional data from published sources in German and French languages that are not widely available are also included. RESULTS: Chemical identification studies showed that PYC is primarily composed of procyanidins and phenolic acids. Procyanidins are biopolymers of catechin and epicatechin subunits which are recognized as important constituents in human nutrition. PYC contains a wide variety of procyanidins that range from the monomeric catechin and taxifolin to oligomers with 7 or more flavonoid subunits. The phenolic acids are derivatives of benzoic and cinnamic acids. The ferulic acid and taxifolin components are rapidly absorbed and excreted as glucuronides or sulphates in men, whereas procyanidins are absorbed slowly and metabolized to valerolactones which are excreted as glucuronides. PYC has low acute and chronic toxicity with mild unwanted effects occurring in a small percentage of patients following oral administration. Clinical studies indicate that PYC is effective in the treatment of chronic venous insufficiency and retinal micro-hemorrhages. PYC protects against oxidative stress in several cell systems by doubling the intracellular synthesis of anti-oxidative enzymes and by acting as a potent scavenger of free radicals. Other anti-oxidant effects involve a role in the regeneration and protection of vitamin C and E. Anti-inflammatory activity has been demonstrated in vitro and in vivo in animals. Protection against UV-radiation-induced erythema was found in a clinical study following oral intake of PYC. In asthma patients symptom scores and circulating leukotrienes are reduced and lung function is improved. Immunomodulation has been observed in both animal models as well as in patients with Lupus erythematosus. PYC antagonizes the vasoconstriction caused by epinephrine and norepinephrine by increasing the activity of endothelial nitric oxide synthase. Dilation of the small blood vessels has been observed in patients with cardiovascular disease, whereas in smokers, PYC prevents smoking-induced platelet aggregation and reduces the concentration of thromboxane. The ability to inhibit angiotensin-converting enzyme is associated with a mild antihypertensive effect. PYC relieves premenstrual symptoms, including abdominal pain and this action may be associated with the spasmolytic action of some phenolic acids. An improvement in cognitive function has been observed in controlled animal experiments and these findings support anecdotal reports of improvement in ADHD patients taking PYC supplements. CONCLUSIONS: There is much evidence showing that PYC has beneficial effects on physiological functions. Results from ongoing clinical research are required to confirm and extend previous observations.

Combined cataract extraction and submacular blood clot evacuation for globe perforation caused by retrobulbar injection.

A 45-year-old woman, originally scheduled for cataract surgery in the left eye, was referred for management of a globe perforation noticed after the retrobulbar injection of an anesthetic solution. There was a moderate degree of vitreous hemorrhage, and initial visual acuity was hand movement. A submacular blood clot of about 4-disc diameter was detected when the vitreous hemorrhage gradually cleared. One week after the incident, combined phacoemulsification, intraocular lens implantation, pars plana vitrectomy, and submacular clot removal using tissue plasminogen activator (tPA) as an adjunct were performed. Recovery was uneventful. At the last follow-up 6 months after surgery, best corrected visual acuity was 20/30.

Role of the indigenous drug saptamrita lauha in hemorrhagic retinopathies.

A clinical study was done on 48 eyes to assess the role of an indigenous drug, Saptamrita Lauha, in the absorption of hemorrhages and prevention of their recurrence in retinopathic eyes. Rapid absorption of retinal hemorrhages was observed in both treated groups: diabetic and hypertensive (mean durations, 16 days and 17.83 days, respectively). In three eyes, the hemorrhage cleared completely; partial clearance was observed in the rest of the eyes. Recurrence of a hemorrhagic episode was less in treated eyes (25% in each group) compared with control eyes (60% in diabetic and 50% in hypertensive patients). This study suggests that Saptamrita Lauha may hasten the process of retinal hemorrhage absorption and prevent its recurrence. The beneficial effect could be attributed to the flavanoid-like properties of one of the ingredients of this natural product.