Combined Corneal Transplant, Glaucoma Drainage Implantation, and Pars Plana Vitrectomy Outcomes in a Pediatric Population.

PURPOSE: The combination of glaucoma drainage device (GDI), pars plana vitrectomy (PPV), and corneal transplantation is well reported in adults. However, little is known about the outcomes of such combined procedures in pediatric patients. We present a retrospective, single-center study to evaluate the safety and outcomes of concurrent GDI and/or PPV with corneal transplantation in patients 18 years and younger. METHODS: Retrospective chart review of pediatric patients (aged 0-18 years) who received either corneal transplants or keratoprosthesis in combination with at least 1 additional procedure (either GDI and/or PPV) at the Illinois Eye and Ear Infirmary, Chicago, IL, between 2003 and 2017. Primary outcomes included vision, intraocular pressure, and cup-to-disc ratio (C/D). Secondary outcomes included the number of repeat surgeries and intraoperative and postoperative complications. RESULTS: Thirty-six patients were included with a mean age of 8.4 years and an average follow-up of 49.7 months. Nineteen patients received corneal surgery, GDI, and PPV; 4 received corneal and GDI surgery; and 13 received corneal and PPV surgery. Of the 19 patients with all 3 procedures, 48% experienced an increase in vision with an average improvement of 0.9 lines at the last follow-up. Intraocular pressure decreased by an average of -7.2 mm Hg for all groups. Fifty-three percent of all patients experienced complications. CONCLUSIONS: Combined keratoplasty, GDI, and PPV seems to be effective in the management of complex pediatric eye disease. However, owing to the high risk of complications in this vulnerable patient population, careful consideration must be taken when determining a patient's surgical candidacy for combined cornea/glaucoma/retina procedures.

Reduced graphene oxide membranes in ocular regenerative medicine.

Biological membranes are currently used in Ophthalmology in order to treat different ocular disorders. These membranes have different properties such as cellular biocompatibility and promoting wound healing. Moreover, intrinsic antimicrobial properties could also be desirable because it would allow their use reducing the risk of infections. Graphene and its derivatives are promising biomaterials that already proved their bactericidal effect. However, their clinical use is limited due to the controversial results regarding their toxicity. In this work, we have developed and characterized a reduced graphene oxide membrane (rGOM) for its use in ocular Regenerative Medicine, and studied its in vitro and in vivo biocompatibility and genotoxicity with different types of human ocular cells. We proved that rGOM allowed the growth of different ocular cells without inducing in vitro or in vivo cytotoxicity or genotoxicity in the short-term. These results indicate that rGOM may be a promising candidate in Regenerative Medicine for the treatment of different ocular pathologies.

Comprehensive genomic diagnosis of inherited retinal and optical nerve disorders reveals hidden syndromes and personalized therapeutic options.

PURPOSE: In the era of precision medicine, genomic characterization of blind patients is critical. Here, we evaluate the effects of comprehensive genetic analysis on the etiologic diagnosis of potentially hereditary vision loss and its impact on clinical management. METHODS: We studied 100 non-syndromic and syndromic Spanish patients with a clinical diagnosis of blindness caused by alterations on the retina, choroid, vitreous and/or optic nerve. We used a next-generation sequencing (NGS) panel (OFTALMOgenics™), developed and validated within this study, including up to 362 genes previously associated with these conditions. RESULTS: We identified the genetic cause of blindness in 45% of patients (45/100). A total of 28.9% of genetically diagnosed cases (13/45) were syndromic and, of those, in 30.8% (4/13) extraophthalmic features had been overlooked and/or not related to visual impairment before genetic testing, including cases with Mainzer-Saldino, Bardet-Biedl, mucolipidosis and MLCRD syndromes. In two additional cases-syndromic blindness had been proposed before, but not specifically diagnosed, and one patient with Heimler syndrome had been misdiagnosed as an Usher case before testing. 33.3% of the genetically diagnosed patients (15/45) had causative variants in genes targeted by clinical trials exploring the curative potential of gene therapy approaches. CONCLUSION: Comprehensive genomic testing provided clinically relevant insights in a large proportion of blind patients, identifying potential therapeutic opportunities or previously undiagnosed syndromes in 42.2% of the genetically diagnosed cases (19/45).

Implantation of a Trifocal Intraocular Lens in High Myopic Eyes with Nasal-Inferior Staphyloma.

PURPOSE: To assess visual outcomes in high myopic eyes with nasal-inferior staphyloma implanted with a pseudophakic trifocal intraocular lens (IOL). METHODS: We retrospectively analyzed the visual outcomes of 50 eyes of 45 patients who had cataract surgery after AT LISA trifocal IOL implantation. Twenty-five eyes diagnosed with posterior staphyloma (nasal-inferior, type IV and V), and 25 eyes as long eyes. Uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA) values were used to assess the efficacy and safety of the surgery. Refraction and defocus curves were also evaluated at 6 months. RESULTS: No intra- or post-operative problems occurred during the 6 months of follow-up. After the surgery, the mean Snellen decimal UDVA ranged from 0.50 to 1.00, and CDVA from 0.60 to 1.00 for both groups. CDVA was 0.91 and 0.74 for the long eye and nasal-inferior staphyloma groups, respectively. Efficacy and safety indexes were 1.22 and 1.32 for the long eye, and 1.26 and 1.43 for the nasal-inferior staphyloma group, respectively. All eyes of both groups showed a postoperative spherical equivalent within ±1.00D. The long eye group showed the highest percentage of spherical equivalent between -0.13D and +0.13D (56%) and the nasal-inferior staphyloma group was between -0.51D and -0.14D (40%). CONCLUSION: The outcomes of the present study show that a trifocal IOL provides good visual acuity in high myopic eyes, being worse for nasal-inferior staphyloma eyes. The degree of tilt of the macular plane is related with the expected visual acuity.

Coenzyme Q10 treatment improved visual field after homonymous quadrantanopia caused by occipital lobe infarction.

PURPOSE: To report the clinical findings and management of a case of occipital lobe infarction with homonymous quadrantanopia in a patient treated with vitamins and coenzyme Q10. OBSERVATIONS: A currently 69-years-old patient presenting in 2007 left inferior quadrantanopia following a right occipital lobe stroke with initial visual field index of 82% and 79% in the right and left eyes, respectively. From 2007 to 2010 was treated with vitamin and antioxidant complexes, without specific signs of changes observed in the visual field (81% right eye, 79% left eye). In 2011 was treated for the first time with coenzyme Q10 (Active complex® Q10 Gold 100 mg) in addition to the vitamin and antioxidant supplementation. A promptly slight improvement of the visual field in both eyes was observed. In 2013, a remarkable improvement was noticed observing a slight scotoma where previously presented the quadrantanopia. Thereafter, in the successive one-year follow-up examinations the patient experienced an exponential improvement in the visual field with gradually fading of the scotoma. Currently the patient no longer presents any sign of quadrantanopia, with normal visual field in both eyes (99% right eye, 98% left eye). CONCLUSION AND IMPORTANCE: Spontaneous improvement more than 6 months after stroke is thought to be unlikely. However, we observed, for the first time, an amelioration of the visual field after 10 years of an occipital lobe stroke. The combination of vitamins and coenzyme Q10 (100 mg) improved the prognosis with significant recovery of the visual field, which is impossible to recover under current knowledge.

Retinal Telemedicine.

PURPOSE OF REVIEW: An update and overview of the literature on current telemedicine applications in retina. RECENT FINDINGS: The application of telemedicine to the field of Ophthalmology and Retina has been growing with advancing technologies in ophthalmic imaging. Retinal telemedicine has been most commonly applied to diabetic retinopathy and retinopathy of prematurity in adult and pediatric patients respectively. Telemedicine has the potential to alleviate the growing demand for clinical evaluation of retinal diseases. Subsequently, automated image analysis and deep learning systems may facilitate efficient processing of large, increasing numbers of images generated in telemedicine systems. Telemedicine may additionally improve access to education and standardized training through tele-education systems. SUMMARY: Telemedicine has the potential to be utilized as a useful adjunct but not a complete replacement for physical clinical examinations. Retinal telemedicine programs should be carefully and appropriately integrated into current clinical systems.

Clinical Decision-Making when Treating Diabetic Macular Edema Patients with Dexamethasone Intravitreal Implants.

Diabetes mellitus (DM) is a metabolic disease frequently associated with comorbidities that include diabetic macular edema (DME). The current medical approach to treating DME involves intravitreal injections with either anti-vascular endothelial growth factors or steroids. However, the burden associated with intravitreal injections and DM-derived complications is high, underlining the need to find optimal treatment regimens. In this article we describe the considerations we apply when treating DME patients with dexamethasone intravitreal implants (Ozurdex®), particularly those that influence the clinical decision-making process during the follow-up period. These considerations are based both on the available medical literature and on our clinical experience following the use of these implants in this type of patient, the goal being to optimize the number of injections and the clinical outcome of this therapy. We also provide a general overview of the pathophysiology of DME, highlighting the inflammatory component as a rationale to use steroids in these patients.

Reduction of foveal bulges and other anatomical changes in fellow eyes of patients with unilateral idiopathic macular hole without vitreomacular pathologic changes.

PURPOSE: To compare the foveal characteristics in fellow eyes (FE) of patients with unilateral idiopathic macular hole without vitreomacular pathologic changes with eyes of healthy controls. METHODS: Forty-seven FE and 52 eyes of 52 age- and sex-matched healthy controls were studied. Quantitative assessment of the dome-shaped appearance of the hyperreflective lines that represent external limiting membrane (ELM_bulge) and inner outer segment junctions (IS/OS_bulge) were made by optical coherence tomography (OCT) images. Inner retinal complex thickness (IRCT) was quantitatively assessed at 1000 and 2000 µm of the foveal center in nasal and temporal quadrants. Presence of alterations in the inner retinal outer layers and central foveal thickness (CFT) were also analyzed. RESULTS: Significantly lower ELM_bulge (p < 0.0001; Mann-Whitney test) and IS/OS_bulge (p < 0.001; student t test) and higher cases with COST alterations, expressed as a diffuse line (p < 0.006; Chi2 test) were found in FE than control eyes. IRCT were significantly reduced in FE at all the studied locations when comparing to control eyes (p < 0.05; student t test), maintaining anatomical proportionality among locations. CONCLUSION: FE without pathologic vitreomacular interactions seems to present some central cone alterations that may be related to other causes than vitreomacular traction.

Metallothionein polymorphisms in a Northern Spanish population with neovascular and dry forms of age-related macular degeneration.

BACKGROUND: To elucidate the potential role of single nucleotide polymorphisms (SNPs) in the metallothionein (MT) genes in Northern Spanish patients with age-related macular degeneration (AMD). METHODS: A total of 130 unrelated Northern Spanish natives diagnosed with AMD (46 dry, 35 neovascular, and 49 mixed) and 96 healthy controls, matched by age and ethnicity, were enrolled in a case-control study. DNA was isolated from peripheral blood and genotyped for 14 SNPs located at 5 MT genes (MT1A: rs11076161, rs 11640851, rs8052394, and rs7196890; MT1B: rs8052334, rs964372, and rs7191779; MT1M: rs2270836 and rs9936741; MT2A: rs28366003, rs1610216, rs10636, and rs1580833; MT3: rs45570941) using TaqMan probes. The association study was performed using the HaploView 4.0 software. RESULTS: The allelic and genotypic frequencies analysis revealed that rs28366003 at MT2A gene is significantly associated with dry AMD. The frequency of genotype AG was significantly higher in dry AMD than in control cases (p = 2.65 × 10-4; AG vs. AA) conferring more than ninefold increased risk to dry AMD (OR = 9.39, 95% CI: 2.11-41.72), whereas the genotype AA confers disease protection (OR = 0.82, 95% CI: 0.71-0.95). No statistically significant differences were observed between AMD subjects and controls in the rest of the 14 SNPs analyzed. CONCLUSIONS: The present study is the first to investigate the potential association of SNPs at MT genes with susceptibility to AMD. We found a significant association of SNP rs28366003 at MT2A gene with susceptibility to the dry form of AMD in a Northern Spanish population.

Blockade of Tumor Necrosis Factor-Alpha: A Role for Adalimumab in Neovascular Age-Related Macular Degeneration Refractory to Anti-Angiogenesis Therapy?

AIMS: To report a case of wet age-related macular degeneration (wet-AMD) refractory to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy in a patient who showed visual and anatomical improvement and stabilization after starting a subcutaneous treatment course with adalimumab, an anti-tumor necrosis factor-alpha (TNF-α) drug, for concomitant Crohn's disease. METHODS: Observational case report of a female patient. Ophthalmological evaluation was performed by slit lamp and ophthalmoscopy (posterior pole and anterior segment). Best-corrected visual acuity (BCVA) was determined, and imaging was performed by fluorescein angiography, indocyanine green angiography, and optical coherence tomography (OCT). Intravitreal therapies used and treatment with anti-TNF-α were recorded. RESULTS: A 64-year-old woman with wet-AMD was treated with fourteen intravitreal injections of ranibizumab (0.5 mg) for a period of 40 months with intervals of 1-6 months. She initially showed a good visual and anatomical response to periodic anti-VEGF treatment but during check visits, anatomical and functional responses deteriorated. At the 40-month follow-up, the patient had developed Crohn's disease, and her rheumatologist started treatment with adalimumab (40 mg subcutaneously every 2 weeks). During the 25 months of treatment with adalimumab, the patient did not require any additional intravitreal anti-VEGF treatments because her BCVA, clinical, and OCT findings improved and remained stable. CONCLUSIONS: We described a case of a patient with wet-AMD refractory to anti-VEGF therapy, which clinically benefited from subcutaneous adalimumab therapy. Treatment with subcutaneous anti-TNF-α in combination with anti-VEGF therapy avoids the high cost and risks related to multiple intravitreal anti-VEGF injections with good functional and anatomic outcomes.

CFH polymorphisms in a Northern Spanish population with neovascular and dry forms of age-related macular degeneration.

PURPOSE: To elucidate the potential role of single-nucleotide polymorphisms (SNPs) in complement factor H (CFH) gene in Northern Spanish patients with age-related macular degeneration (AMD). METHODS: A case-control study of 130 unrelated native Northern Spanish diagnosed with AMD (46 dry, 35 neovascular and 49 mixed) and 96 healthy controls matched by age and ethnicity were enrolled. DNA was isolated from peripheral blood and genotyped for AMD-associated SNPs (rs3753394, rs529825, rs800292, rs3766404, rs203674, rs10671170, rs3753396 and rs1065489) using TaqMan probes and restriction fragment length polymorphism (RFLP). The association study was performed using the HaploView 4.0 software. RESULTS: The allelic frequency analysis revealed that rs529825, rs800292, rs203674 and rs10671170 were significantly associated with an increased risk for AMD. The haplotypes CGG (rs3753394, rs529825 and rs800292) and GCAG (rs203674, rs1061170, rs3753396 and rs1065489) were significantly associated with AMD while the haplotypes CAA (rs3753394, rs529825 and rs800292) and TTAG (rs203674, rs1061170, rs3753396 and rs1065489) were found to be protective. Small differ-ences in allelic frequencies were found between dry and neovascular cases; however, these differences were not significant and did not distinguish one form the other. CONCLUSIONS: This study found significant association of SNPs rs529825, rs800292, rs203674 and rs1061170 in the CFH gene with susceptibility to AMD. We identified haplotypes that confer protection or increased risk of AMD but not specific genetic variants in CFH capable to distinguish the different clinical forms of AMD in this cohort. Collectively, our results confirmed that CFH represents a strong genetic risk factor for this disease in the Northern Spanish population.