Quality of life in keratoconus: evaluation with Keratoconus Outcomes Research Questionnaire (KORQ).

To assess the quality of life of keratoconus patients using the Keratoconus Outcomes Research Questionnaire (KORQ), translated and validated in Portuguese language. The KORQ is the only validated keratoconus specific questionnaire and has a high rating for its psychometric properties. This cross-sectional study enrolled 100 keratoconus patients from a tertiary referral eye hospital between April 2018 and June 2019. Associations between age, sex, allergic conjunctivitis, keratoconus stage, best-corrected visual acuity (BCVA), maximum simulated keratometry (Kmax), steep keratometry (K2), pachymetry, treatments performed, hydrops, and KORQ scores were evaluated using univariate (Wilcoxon test and the Kruskal Wallis test) and multivariate linear regression with stepwise backward modeling. Lower KORQ scores are associated with better quality of life, whereas, higher scores are associated with greater impairment of functional activities and symptoms. Among the 100 patients, mild, moderate, and severe keratoconus were observed in 15%, 46% and 39% of participants, respectively. Univariate analysis showed lower function scores values, with male sex (p < 0.05) and both functional and symptom scores were significantly associated with BCVA < 0.3 (LogMAR) (p < 0.05). Multivariate analysis indicated significantly lower functional scores in individuals with BCVA < 0.3 (LogMAR) (p < 0.001) and those with a history of crosslinking treatment (p = 0.022), while symptom scores were only significantly associated with only BCVA < 0.3 (LogMAR) (p < 0.001). In patients with keratoconus, BCVA in the better eye and history of crosslinkig were factors associated with better quality of life scores using the KORQ.

Late ophthalmology findings in a X-linked juvenile retinoschisis patient / Achados oftalmológicos tardios em um paciente portador de retinosquise juvenil ligada ao cromossomo X

ABSTRACT X-linked juvenile retinoschisis (XLRS) is a vitreoretinal degeneration caused by mutations in the RS1 gene, generally characterized by bilateral maculopathy and peripheral retinoschisis leading to progressive visual loss during the first 2 decades of life and complications like retinal detachment and vitreous hemorrhage. Herein, we present late ophthalmology findings in a XLRS patient.

RESUMO A retinosquise juvenil ligada ao cromossomo X (XLRS) é uma degeneração vitreorretiniana causada por mutações no gene RS1, geralmente caracterizada por maculopatia bilateral e retinosquise periférica, levando à perda visual progressiva durante as primeiras 2 décadas de vida e complicações como descolamento de retina e hemorragia vítrea. Apresentamos aqui achados oftalmológicos tardios em um paciente com XLRS.

Acadesine suppresses TNF-α induced complement component 3 (C3), in retinal pigment epithelial (RPE) cells.

RATIONALE: Age-related macular degeneration (AMD) is the most prevalent form of irreversible blindness in the developed world. Aging, inflammation and complement dysregulation affecting the retinal pigment epithelium (RPE), are considered significant contributors in its pathogenesis and several evidences have linked tumor necrosis factor alpha (TNF-α) and complement component 3 (C3) with AMD. Acadesine, an analog of AMP and an AMP-activated protein kinase (AMPK) activator, has been shown to have cytoprotective effects in human clinical trials as well as having anti-inflammatory and anti-vascular exudative effects in animals. The purpose of this study was to evaluate if acadesine is able to suppress TNF-α induced C3 in RPE cells. METHODS: ARPE-19 and human primary RPE cells were cultured and allowed to grow to confluence. TNF-α was used for C3 induction in the presence or absence of acadesine. Small molecule inhibitors and siRNA were used to determine if acadesine exerts its effect via the extracellular or intracellular pathway and to evaluate the importance of AMPK for these effects. The expression level of C3 was determined by immunoblot analysis. RESULTS: Acadesine suppresses TNF-α induced C3 in a dose dependent manner. When we utilized the adenosine receptor inhibitor dipyridamole (DPY) along with acadesine, acadesine's effects were abolished, indicating the necessity of acadesine to enter the cell in order to exert it's action. However, pretreatment with 5-iodotubericidin (5-Iodo), an adenosine kinase (AK) inhibitor, didn't prevent acadesine from decreasing TNF-α induced C3 expression suggesting that acadesine does not exert its effect through AMP conversion and subsequent activation of AMPK. Consistent with this, knockdown of AMPK α catalytic subunit did not affect the inhibitory effect of acadesine on TNF-α upregulation of C3. CONCLUSIONS: Our results suggest that acadesine suppresses TNF-α induced C3, likely through an AMPK-independent pathway, and could have potential use in complement over activation diseases.

Neuroprotective effects and mechanisms of action of nicotinamide mononucleotide (NMN) in a photoreceptor degenerative model of retinal detachment.

Currently, no pharmacotherapy has been proven effective in treating photoreceptor degeneration in patients. Discovering readily available and safe neuroprotectants is therefore highly sought after. Here, we investigated nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD+), in a retinal detachment (RD) induced photoreceptor degeneration. NMN administration after RD resulted in a significant reduction of TUNEL+ photoreceptors, CD11b+ macrophages, and GFAP labeled glial activation; a normalization of protein carbonyl content (PCC), and a preservation of the outer nuclear layer (ONL) thickness. NMN administration significantly increased NAD+ levels, SIRT1 protein expression, and heme oxygenase-1 (HO-1) expression. Delayed NMN administration still exerted protective effects after RD. Mechanistic in vitro studies using 661W cells revealed a SIRT1/HO-1 signaling as a downstream effector of NMN-mediated protection under oxidative stress and LPS stimulation. In conclusion, NMN administration exerts neuroprotective effects on photoreceptors after RD and oxidative injury, suggesting a therapeutic avenue to treating photoreceptor degeneration.

Corneal Collagen Cross-Linking in Young Patients for Progressive Keratoconus.

PURPOSE: The goal of this study was to compare the effect of early corneal collagen cross-linking (CXL) intervention (before 17 years of age) with that of late intervention (after 17 years of age) on the characteristics and progression of keratoconus. PATIENTS AND METHODS: One hundred five eyes of 94 patients with keratoconus undergoing treatment with CXL were included. The patients were divided into 2 groups by age: group 1 (mean age of 13.8 yrs; range 10-16) and group 2 (mean age of 21.5 yrs; range 17-36). Eyes were evaluated regarding best-corrected visual acuity (BCVA), refractive error, corneal endothelial cell density, and central corneal thickness, as well as using slit-lamp biomicroscopy, Goldmann tonometry, and the keratometry (Kmax, Ksteep, and Kflat parameters) test before CXL and at 1, 3, 6, and 12 months thereafter. RESULTS: The mean (SD) BCVA of group 1 was 0.45 (±0.25) before CXL and 0.56 (±0.29) 1 year after CXL (P = 0.030); mean (SD) Kmax, Ksteep, and Kflat were 58.47 (±7.2), 52.93 (±5.4), 47.22 (±4.2) before CXL respectively, and 58.21 (±7.7), 52.25 (±5.5), and 46.56 (±4.6) 1 year after CXL, respectively (P = 0.897, 0.481, and 0.491). The mean (SD) BCVA of group 2 was 0.50 (±0.30) before CXL and 0.56 (±0.32) 1 year thereafter (P = 0.346); mean (SD) Kmax, Ksteep, and Kflat were, respectively, 57.64 (±7.1), 54.02 (±6.2), and 48.60 (±4.1) before CXL and 56.46 (±8.0), 52.46 (±5.8), and 47.85 (±4.9) 1 year after CXL, respectively (P = 0.553, 0.258, and 0.640). CONCLUSIONS: The study showed no statistical differences between younger and older patients. These findings support the indication of CXL treatment in pediatric patients for early stabilization of the disease and better progress regarding BCVA and keratometry parameters.

NLRP3 inflammasome in NMDA-induced retinal excitotoxicity.

N-methyl-D-aspartate (NMDA)-induced excitotoxicity is an acute form of experimental retinal injury as a result of overactivation of glutamate receptors. NLRP3 (nucleotide-binding domain, leucine-rich-repeat containing family, pyrin domain containing-3) inflammasome, one of the most studied sensors of innate immunity, has been reported to play a critical role in retinal neurodegeneration with controversial implications regarding neuroprotection and cell death. Thus far, it has not been elucidated whether NMDA-mediated excitotoxicity can trigger NLRP3 inflammasome in vivo. Moreover, it is unknown if NLRP3 is beneficial or detrimental to NMDA-mediated retinal cell death. Here, we employed a murine model of NMDA-induced retinal excitotoxicity by administering 100 nmoles of NMDA intravitreally, which resulted in massive TUNEL+ (TdT-dUTP terminal nick-end labelling) cell death in all retinal layers and especially in retinal ganglion cells (RGCs) 24 h post injection. NMDA insult in the retina potentiates macrophage/microglia cell infiltration, primes the NLRP3 inflammasome in a transcription-dependent manner and induces the expression of interleukin-1ß (IL-1ß). However, despite NLRP3 inflammasome upregulation, systemic deletion of Nlrp3 or Casp1 (caspase-1) did not significantly alter the NMDA-induced, excitotoxicity-mediated TUNEL+ retinal cell death at 24 h (acute phase). Similarly, the deletion of the two aforementioned genes did not alter the survival of the Brn3a+ (brain-specific homeobox/POU domain protein 3A) RGCs in a significant way at 3- or 7-days post injection (long-term phase). Our results indicate that NMDA-mediated retinal excitotoxicity induces immune cell recruitment and NLRP3 inflammasome activity even though inflammasome-mediated neuroinflammation is not a leading contributing factor to cell death in this type of retinal injury.

Macular phototoxicity after corneal cross-linking.

PURPOSE: To assess potential vascular, structural, and functional changes to the macula in patients with keratoconus that underwent ultraviolet A (UVA)-riboflavin-mediated corneal collagen cross-linking (CXL) therapy. PATIENTS AND METHODS: Seventeen eyes from 17 patients of age 16 years or older with keratoconus undergoing CXL treatment were studied. The same eye served as its own control (before CXL vs after CXL). Eyes were evaluated in terms of best-corrected visual acuity (BCVA), refractive error, intraocular pressure, Amsler grid, retinography, fluorescein angiography, autofluorescence, and spectral domain optical coherence tomography (SD-OCT) prior to CXL and 7 and 30 days after treatment. Multifocal electroretinography (mfERG) was recorded prior to and 7 days after CXL. RESULTS: Mean (SD) BCVA by logMAR chart was 0.47 (±0.12) pre-CXL, 0.55 (±0.15) 7 days post-CXL (P=0.57), and 0.46 (±0.10) 30 days post-CXL (P=0.87). Mean (SD) SD-OCT central macular thickness (µm) was 253.62 (±20.9) pre-CXL, 260.5 (±18.7) 7 days post-CXL (P=0.48), and 256.44 (±21.6) 30 days post-CXL (P=0.69). In 12 eyes, mfERG revealed a statistically significant increase (P=0.0353) in P1 latency (ms) of ring four from the pre-CXL period (39.45±2.05) to 7 days post-CXL (41.04±1.28) period. Regression analysis showed that the increase in P1 latency was correlated with the increase in central macular thickness (P=0.027). Furthermore, nine patients experienced a significant decrease in P1 amplitudes of rings 1 (P=0.0014), 2 (P=0.0029), 3 (P=0.0037), 4 (P=0.0014), and 5 (P=0.0012) from pre-CXL to 7 days post-CXL. Conclusion: In this pilot study, most of the patients exhibited slight changes in their mfERG parameters and OCT thickness, despite a lack of vascular abnormalities observed on fluorescein angiography/autofluorescence imaging, no alteration in BCVA, and no reports of symptoms. These changes could, therefore, be categorized as a mild subclinical effect of the corneal cross-linking procedure.

Repeated penetrating corneal transplantation in patients with a previous tectonic transplant / Retransplante penetrante de córnea em pacientes submetidos à transplante tectônico prévio

ABSTRACT Objective: To analyze, in a university hospital of reference, the rate of a new penetrating corneal transplantation in patients that had previously undergone a tectonic keratoplasty and analyze the results after one year of surgery. Methods: Retrospective review of patients undergoing penetrating corneal transplantation, from november of 2010 to november of 2014. Comparative analysis of best corrected visual acuity (BCVA), intraocular pressure and corneal transparency before surgery and after one year, in the group of patients in which it was performed a re-graft after a failed tectonic transplantation. Results: A total of 318 patients underwent penetrating corneal transplantation during the study period. Of the 199 patients who underwent tectonic transplantation, 36 were subjected to re-graft and re-grafts were performed more than once in 2 eyes, with total of 38 transplants (19,09%). The results showed improvement of BCVA in 20 (52.63%), worsening in 8 (21.05%) and unchanged in 10 (26.31%); improvement of intraocular pressure in 3 (7.89%), deterioration in 3 (7.89%) and unchanged in 32 (84.21%); improvement of corneal transparency 25 (65.78%), worsening 4 (10.52%) and 9 unchanged (23.68%) patients. Conclusion: This study demonstrated a considerable number of repeated penetrating keratoplasty in patients with a history of failed tectonic corneal transplantation. In spite of bad prognosis in cases where there is high-risk corneal recipients and history of a failed tectonic transplant, there was improvement of the corneal transparency and best corrected visual acuity even after a year of surgery.

RESUMO Objetivo: Analisar, em um hospital universitário de referência, a taxa de novo transplante penetrante de córnea em pacientes que já haviam realizado um transplante de córnea tectônica e analisar os resultados após um ano de cirurgia. Métodos: Análise retrospectiva dos prontuários de pacientes submetidos a transplante de córnea penetrante, a partir de novembro de 2010 a novembro de 2014. A análise comparativa da melhor acuidade visual corrigida, pressão intraocular e de transparência da córnea antes da cirurgia e após um ano, no grupo de pacientes em que foi realizado um retransplante após um transplante tectônico falho. Resultados: Foram avaliados 318 pacientes submetidos à ceratoplastia penetrante no período estudado. Dos 199 pacientes que realizaram transplante tectônico, 36 foram submetidos a re-enxerto e re-enxertos foram realizados mais de uma vez em 2 olhos, com total de 38 transplantes (19,09%). A análise dos resultados mostrou melhora da melhor acuidade visual corrigida em 20 (52,63%), piora em 8 (21,05%) e inalterado em 10 (26,31%); melhora da pressão intraocular em 3 (7,89%), piora em 3 (7,89%) e inalterado em 32 (84,21%); melhora da transparência corneana em 25 (65,78%), piora em 4 (10,52%) e inalterado em 9 (23,68%) pacientes. Conclusão: O estudo demonstrou um número considerável de retransplante penetrante de córnea em pacientes com história de transplante de córnea tectônico falho. Apesar do mau prognóstico nos casos com história de um transplante tectônico falho, houve melhora da transparência da córnea e da acuidade visual mesmo após um ano da cirurgia.