Despigmentação precoce em caso de ceratopigmentação / Early depigmentation in case of keratopigmentation

RESUMO A ceratopigmentação teve seu primeiro registro pelo filósofo Galeno há muitos séculos como uma estratégia utilizada para o tratamento estético de pacientes com leucomas. As córneas com leucoma são patológicas e, muitas vezes, intolerantes a lentes de contato cosméticas ou próteses oculares, sendo comum a queixa de desconforto excessivo, proporcionado pela superfície corneana irregular. Assim, a ceratopigmentação é uma alternativa para a melhora estética de pacientes com opacidades corneanas. Descrevemos o caso de um paciente do sexo masculino, 39 anos, que apresentou despigmentação precoce em caso de ceratopigmentação associado a quadro de ceratite herpética necrotizante. O paciente foi submetido ao tratamento com aciclovir 2g ao dia e doxiciclina 200mg ao dia, evoluindo com melhora do quadro clínico, apesar da má adesão medicamentosa.

ABSTRACT Keratopigmentation was first recorded many centuries ago by the philosopher Galeno, as a strategy used for the aesthetic treatment of patients with leukomas. Corneas with leucoma are pathological and often intolerant of cosmetic contact lenses or ocular prostheses, with complaints of excessive discomfort provided by the irregular corneal surface being common. Therefore, keratopigmentation is an alternative for the aesthetic improvement of patients with corneal opacities. We describe the case of a 39-year old male patient, who presented early depigmentation in a case of keratopigmentation associated with necrotizing herpetic keratitis. The patient was treated with Acyclovir 2g/day and Doxycycline 200mg/day, evolving with clinical improvement, despite poor medication adherence.

Risk of induction of corneal neovascularization with topical erythropoietin: an animal safety study

Purpose: To evaluate the pro-angiogenic effect of topical erythropoietin on cornea in chemical burn-injured rabbit eyes. Methods: The corneal alkali-burn injury was induced in 10 eyes of 10 rabbits using filter paper saturated with 1.0 mol sodium hydroxide. The eyes were categorized into the treatment group (n = 5) that received topical erythropoietin (3000 IU/mL) every 8 hr for one month versus the control group (n = 5) that received normal saline every 8 hr for one month. All eyes were treated with topical ciprofloxacin every 8 hr until corneal re-epithelialization was complete. Corneal epithelial defects, stromal opacity, and neovascularization were evaluated after the injury. At the conclusion of the study, the rabbits were euthanized and their corneas were submitted to histopathological examination. Results: Baseline characteristics including the rabbits' weight and the severity of corneal injury were comparable in two groups. Time to complete corneal re-epithelialization was 37 days in the treatment group and 45 days in the control group (P = 0.83). There was no significant difference between the groups in the rate of epithelial healing or corneal opacification. Clinical and microscopic corneal neovascularization was observed in one eye (20%) in the treatment group and two eyes (40%) in the control group (P = 0.49). Conclusion: Recombinant human erythropoietin administered topically did not induce vessel formation in rabbit corneas after chemical burn.

Terapias actuales en la vascularización corneal / Current therapies in corneal vascularization

Una córnea transparente es esencial para una excelente visión; es por eso que es avascular. Pero existen condiciones que favorecen la invasión de neovasos al tejido corneal, como infecciones, inflamación, hipoxia, trauma, entre otras, que reducen la calidad visual y en algunos casos llegan hasta la pérdida de esta. La neovascularización corneal representa un problema importante de salud pública a nivel mundial. Se realizó una búsqueda automatizada con el objetivo de encontrar información actualizada sobre el tratamiento de la neovascularización corneal, para lo cual se utilizó la plataforma infomed. La información se resumió en el documento final. Sobre el tema, existe un progreso notable en el entendimiento de la patogénesis, el mejoramiento y la seguridad de los nuevos tratamientos. Los corticoesteroides y los agentes anti-VEGF (factor de crecimiento endotelial vascular) continúan siendo los medicamentos de primera línea, usados principalmente para evitar la formación de los nuevos vasos, no así para vasos maduros, donde la mejor opción son los procedimientos quirúrgicos o combinados. Se necesitan más estudios experimentales, y los ya existentes deben ser utilizados en ensayos clínicos para investigar sobre la dosis segura y los efectos secundarios, y así encontrar terapias radicales, más eficaces, que le den a los pacientes con neovascularización corneal la esperanza de una mejor calidad visual(AU)

A clear cornea is essential for excellent vision; that is why it is avascular. But there are conditions that favor the invasion of neovessels into the corneal tissue, such as infections, inflammation, hypoxia, trauma, among others, which reduce visual quality and in some cases even lose it. Corneal neovascularization represents a major public health problem worldwide. An automated search was carried out in order to find updated information on the treatment of corneal neovascularization, for which the infomed platform was used. The information was summarized in the final document. On the subject, there is notable progress in understanding the pathogenesis, improvement and safety of new treatments. Corticosteroids and anti-VEGF (vascular endothelial growth factor) agents continue to be the first-line drugs, used mainly to prevent the formation of new vessels, not for mature vessels, where the best option is surgical or combined procedures. More experimental studies are needed; and the existing ones should be used in clinical trials to investigate the safe dose and side effects, and thus find radical and more effective therapies that give patients with corneal neovascularization the hope of better visual quality(AU)

A Case of Streptococcus dysgalactiae Endophthalmitis after Cataract Surgery

PURPOSE: To report the first case of endophthalmitis due to Streptococcus dysgalactiae after phacoemulsification and posterior chamber intraocular lens implantation in the Republic of Korea. CASE SUMMARY: A 65-year-old male was transferred because of endophthalmitis following cataract surgery. His initial visual acuity was light perception. Because inflammation of the anterior chamber and vitreous cavity progressed rapidly, we performed total pars planar vitrectomy and intraocular lens extraction in addition to administering intravitreal antibiotics and intravitreal dexamethasone injections. Streptococcus dysgalactiae was identified in samples cultured from the vitreous and anterior chamber fluid. Four days after surgery, we washed the anterior chamber and intravitreal antibiotics were again injected because of increased inflammation of the anterior chamber and vitreous. The patient was discharged 25 days after surgery but corneal neovascularization, contraction, edema, infiltration, and hypopyon remained. Visual acuity progressed to no light perception and there was shrinkage of the globe. CONCLUSIONS: Endophthalmitis due to Streptococcus dysgalactiae is very rare. We report the first case of endophthalmitis caused by Streptococcus dysgalactiae in the Republic of Korea. The prognosis for recovery was poor despite aggressive treatment.

The Therapeutic Effect of Sclerocorneal Lens in Coexisting Corneal Ectasia and Stevens-Johnson Syndrome

PURPOSE: We report short-term treatment effects of a mini-scleral lens in patients with Stevens-Johnson syndrome and corneal ectasia. CASE SUMMARY: A 54-year-old female who had been diagnosed with Stevens-Johnson syndrome and keratoconus presented with persistent right eye pain and decreased visual acuity. Therapeutic lenses, topical antibiotic eye drops, and topical steroid eye drops were used; however the symptoms were not controlled, then the patient was treated with a mini-scleral contact lens in the right eye. At the time of the first visit to our hospital 17 years ago, and the best-corrected visual acuity (BCVA) of the right eye was logMAR 0.22. However, Stevens-Johnson syndrome and corneal ectasia were severe and cataract surgery was considered because of worsening cataracts, but the patients refused this surgery. At the time, the BCVA of the right eye was then reduced to logMAR 1.10. On ophthalmic examination, there was conjunctival fibrosis and corneal neovascularization of the right eye. The symptoms were not managed with a using a therapeutic lens, and then the patient was prescribed a mini-scleral contact lens. After wearing the mini-scleral contact lens, the corneal and conjunctival neovascularization was reduced. After 6 months, the BCVA of the right eye improved to logMAR 0.60. CONCLUSIONS: In patients with Stevens-Johnson syndrome and corneal ecstasia, mini-scleral contact lens can be considered as a useful treatment option for visual improvement and symptom control.

Corneal angiogenesis based on different protocols of alkaline cauterization in murine models

Abstract Purpose: To establish and compare protocols of alkaline cauterization for inducing corneal angiogenesis in murine models. Methods: Twenty-four adult Wistar rats were distributed into four groups (G1, G2, G3, and G4). The right eye cornea from each rat was cauterized using filter paper (3 mm), soaked in a solution of silver and potassium nitrates (3:1). Cauterization times were 10 (G1 and G4), or 20 seconds (G2 and G3). Cauterized corneas were washed with Ringer's lactate solution. The filter paper was either removed before washing (G1 and G2), or kept on the corneas (G3 and G4). Corneas were photographed at multiple time points (2, 4, 6, 8, 11, 13, and 15 days after the procedure), and neovascularization parameters were assayed. Results: Neovascularization was observed in 66% of G1 corneas, and 100% of G2, G3, and G4 corneas. On day 15, G1 corneas showed smaller vascularized areas (12.63 ± 12.59%) compared to those in the G3 (41.95 ± 17.32%) and G4 (33 ± 11.74%) (P < 0.05) groups. Conclusions: The silver and potassium nitrate solution effectively induced corneal angiogenesis. The G2, G3, and G4 protocols showed excellent reproducibility, and induced vascularization in 100% of corneas.

Effects of topical and subconjunctival use of bevacizumab on corneal neovascularization in rabbits' eyes / Efeitos do uso tópico e subconjuntival do bevacizumabe na neovascularização corneana de olhos de coelhos

ABSTRACT Purpose: To evaluate and compare the effects of topical application and subconjunctival injection of bevacizumab on corneal neovascularization (CNV) in rabbits' eyes after chemical burning of the cornea. Methods: The animals were randomly distributed into four groups of five animals. In one group, the drug was instilled, while in another, it was administered by subconjunctival injection. The two procedures using bevacizumab were compared with instillation and subconjunctival injection of saline solution (S). Neovascularization was evaluated according to the size of the invasion area of new blood vessels and through computerized analysis of this area. The data were analyzed using the Kruskal-Wallis test followed by Dunn's test for two-by-two comparison of the groups, to assess the external examination of CNV. Analysis of variance was used to assess the area of CNV. P<0.05 was considered statistically significant. Results: Assessing both the external examination and the invasion area of neovessels on the 5th and 10th days, there was a clear difference between the groups. The group to which saline solution had been applied showed higher scores for CNV, as well as increases in the invasion area of neovessels. Two-by-two comparison of groups revealed no significant differences. However, an analysis of the factors involved (injection vs. instillation and bevacizumab vs. saline solution) showed that injection did not differ from instillation, but that bevacizumab differed from saline solution. Conclusion: Bevacizumab showed an inhibitory effect on CNV in rabbits' eyes after chemical burning of the cornea. There was no difference between the topical or subconjunctival administration of bevacizumab in the inhibition of CNV.

RESUMO Objetivos: Avaliar e comparar o efeito do uso tópico e da injeção subconjuntival do bevacizumabe na neovascularização corneana de olhos de coelhos após queimadura química. Métodos: Os animais foram distribuídos de forma aleatória em quatro grupos de cinco animais. Em um grupo de coelhos a droga foi instilada, enquanto em outro foi aplicada injeção subconjuntival, sendo os dois procedimentos comparados com a instilação e injeção subconjuntival de soro fisiológico 0,9% (SF) e entre si. A neovascularização foi avaliada conforme o tamanho da área de invasão dos neovasos e com análise computadorizada da mesma. Na análise de dados aplicou-se o teste de Kruskal-Wallis seguido do teste de Dunn com p<0,05 para comparação dos grupos dois a dois na análise do exame externo da neovascularização corneana. Na análise da área de neovascularização corneana, aplicou-se o teste F de análise de variância. A significância estatística foi definida como valor de p<0.05. Resultados: A avaliação do exame externo e da área de invasão de neovasos, no 5º e 10º dia, mostrou nítida diferença entre os grupos. Com o uso de soro fisiológico houve maior graduação na escala de neovascularização corneana e também na área de invasão dos nevasos, o que demonstrou o efeito inibitório do bevacizumabe. Nas comparações dos grupos dois a dois não foram detectadas diferenças significativas, porém, ao analisar os fatores envolvidos (procedimentos: injeção ou instilação, e as drogas: bevacizumabe ou soro fisiológico), verificou-se que a injeção não diferiu da instilação, mas o bevacizumabe diferiu do soro fisiológico. Conclusão: O bevacizumabe apresentou efeito inibitório na neovascularização corneana de olhos de coelhos após queimadura química, tanto por via tópica como por via subconjuntival e não houve diferença entre a via tópica e a via subconjuntival de administração do bevacizumabe na inibição da neovascularização corneana.

Two Cases of Corneal Neovascularization Improved by Electrocauterization and Subconjunctival Bevacizumab Injection

PURPOSE: To report an experience of improving symptoms through treatment with electrocauterization and subconjunctival bevacizumab injection in two patients with keratitis accompanied by corneal neovascularization and opacity. CASE SUMMARY: (Case 1) A 20-year-old woman visited our institution complaining of binocular blurred vision and congestion for the previous 3 years. Her best corrected visual acuity (BCVA) was 0.07 in the right eye and 0.4 in the left eye (Han Chun-suk visual acuity chart, decimal). The diagnosis was bilateral rosacea keratitis. Antibiotics, steroid eye drops and oral antibiotics were administered, but no improvement was observed. Electrocauterization was performed at the origin of the neovascularization of the cornea and bevacizumab was injected at the peripheral subconjunctiva in the right eye. Thereafter the corneal neovascularization did not recur, corneal opacity was reduced, and BCVA improved to 0.5. (Case 2) A 19-year-old woman visited complaining of left eye congestion for the previous 3 years. Her BCVA was 1.0 in the right eye and 0.08 in the left eye.The diagnosis was phlyctenular keratitis of the left eye. Antibiotics, steroid eye drops and oral antibiotics were administered, but no improvement was observed. Therefore, electrocauterization and subconjunctival bevacizumab injection were performed in the cornea of the left eye, after which corneal neovascularization and opacity decreased. CONCLUSIONS: In these cases, we report improvement of symptoms after treatment with electrocauterization and subconjunctival bevacizumab injection after failed treatment of palpebral sanitation, antibiotic and steroid.

Degeneración nodular de Salzmann / Salzmann's nodular degeneration

La degeneración nodular de Von Salzmann constituye una entidad clínico-patológica en la que aparecen nódulos lisos y opacos, blanco grisáceos o algo azulados en las capas anteriores de la córnea. La afectación suele ser bilateral y los nódulos tienden a disponerse en anillo sobre la media periferia corneal. Pueden estar relacionados o no con un proceso inflamatorio previo y su tratamiento puede ser sintomático o quirúrgico si compromete el área pupilar y con ella la visión del paciente.Se presenta un paciente masculino, de 57 años de edad, coloración de la piel blanca, quien acudió a la consulta y refirió enrojecimiento de ambos ojos (predominio del ojo derecho), con picor, escozor y lagrimeo, de más de 6 meses de evolución. Asociado a esto notó una zona de color blanquecina en ambos ojos. En la exploración oftalmológica se observaron lesiones blanquecinas sobrelevadas de aspecto hialino, en el tercio inferior de la córnea en el ojo derecho y en el ojo izquierdo hacia la región nasal. Se concluye que el caso presenta una degeneración nodular de Salzmann(AU)

Von Salzmann nodular degeneration constitutes a clinical pathological condition in which flat and opaque, white-grayish or bluish nodules appear in the anterior layers of the cornea. The effect is usually bilateral and the nodules tend to spread in a ring form upon the corneal peripheral media. It can be related or not with previous inflammatory process and its treatment can be symptomatic or surgical if the papillary area and the patient's vision are compromised. Here is the case of a 57 years-old male Caucasian patient, who went to the doctor´s and complained of reddened eyes (mainly the right eye), itching and tearing for more than six months. In addition to this, he observed a whitish area in both eyes. The eye screening showed overelevated whitish lesions of hyaline aspect in the lower third of the right eye cornea and in the left eye towards the nasal region. It was concluded that this is a case of Von Salzmann nodular degeneration(AU)

A linfangiogênese em enxertos corneanos humanos que evoluem para retransplante / Lymphangiogenesis in human corneal grafts that has evolved to re-transplantation

RESUMO Objetivo: Estudar botões corneanos humanos com linfangiogênese através do exame histopatológico, juntamente com os enxertos de seus transplantes anteriores e posteriores, avaliando os intervalos de tempo para sucessivas cirurgias. Métodos: Estudo descritivo, observacional, longitudinal de botões corneanos humanos com linfangiogênese, juntamente com seus transplantes anteriores e posteriores. Os tecidos foram provenientes de ceratoplastia penetrante no período compreendido entre os anos 2006 e 2013. Após revisão de prontuários em que foram obtidas principalmente as datas das cirurgias, construímos uma tábua de sobrevivência a partir da qual os intervalos de tempo para retransplante foram calculados. Resultados: Entre 89 casos de linfangiogênese corneana, foram incluídos apenas aqueles 22 que possuíam registros no prontuário de transplantes anteriores ou posteriores. Nos casos que apresentavam como provável etiologia do retransplante a linfangiogênese, isolada ou associada à hemangiogênese (grupos pré-linfangiogênese/linfangiogênese e interlinfangiogênese), foram encontrados intervalos de tempo para retransplante menores (7 e 3 meses, respectivamente) que aquele encontrado no grupo linfangiogênese/pós-linfangiogênese que apresentava outras etiologias prováveis para os retransplantes (11,31 meses). Casos que apresentavam como etiologia provável do retransplante a linfangiogênese isolada apresentaram um intervalo para retransplante (3 meses) ainda menor que aquele encontrado nos casos em que a etiologia provável era a linfangiogênese associada à hemangiogênese (7,80 meses). Conclusão: Linfangiogênese, isolada ou associada à hemangiogênese, foi encontrada nos enxertos corneanos humanos estudados que evoluíram para retransplante em pequenos intervalos de tempo. Esse achado nos leva a sugerir um possível papel para os vasos linfáticos na redução do tempo de sobrevida dos enxertos corneanos humanos.

ABSTRACT Objective: To study human corneal buttons with lymphangiogenesis through histopathological examination, together with the grafts of their preceding and subsequent transplantations, evaluating the time intervals for successive surgeries Methods: A descriptive, observational and longitudinal study of human corneal buttons that have lymphatic vessels, together with its preceding and subsequent transplants. Tissues were obtained from penetrating keratoplasty in the period between the years 2006 and 2013. After a medical records review in which information on the dates of the surgeries were mainly obtained, we built a survival table from which the time intervals for retransplantation were calculated. Results: Among 89 cases of corneal lymphangiogenesis, we included only those 22, which had previous or subsequent transplantations records in medical records. In cases where the probable regrafting etiology were lymphangiogenesis, alone or combined with hemangiogenesis (pre-lymphangiogenesis/lymphangiogenesis and interlymphangiogenesis groups), time intervals for retransplantation were found to be minor (7 and 3 months, respectively) than that found in lymphangiogenesis/post-lymphangiogenesis group that had other probable etiologies for retransplantations (11.31 months). Cases that had isolated lymphangiogenesis as probable etiology of retransplantation showed an interval time for retransplantation (3 months) lower than that found in cases in which the probable etiology was lymphangiogenesis associated with hemangiogenesis (7.80 months). Conclusion: Lymphangiogenesis, alone or combined with hemangiogenesis, was found in human corneal grafts studied that have evolved to regraft in small time intervals. This finding leads us to suggest a possible role for the lymphatic vessels in reducing the human corneal grafts survival time.

The main findings in histopathological examination of human corneal buttons with lymphangiogenesis / Principais achados do exame histopatológico de botões corneanos humanos com linfangiogênese

Objective: To detect the presence of lymphatic vessels in the cornea through histopathological examination, trying to identify findings that are most commonly found with the presence of these vessels in this tissue. Methods: Retrospective descriptive study of human corneal buttons with lymphangiogenesis. Tissues were obtained from penetrating keratoplasty in the period between the years 2006 and 2013. A medical record review was conducted looking for information about sex, age and graft etiology. Results: 89 corneal buttons were included, out of which 37 were from female patients and 52 were from male patients. The average age was 47.70 ± 23.95 years (mean ± SD). Lymphangiogenesis was found mainly associated with hemangiogenesis. However, isolated lymphangiogenesis was observed in 28 (31.46%) patients. In 18 (20.22%) cases were found an amount of lymphatic vessels approximately four times higher than that found in most part of the sample. A lot of cases were found in inflammatory conditions such as infection and perforation. Near the lymphangiogenesis, we found many cases of anterior synechia and myofibroblasts. In 17 (16.35%) cases, no change was observed in the vicinity of corneal lymphatic vessels. Conclusions: We demonstrated through a histopathological examination, that findings admittedly associated with lymphangiogenesis like inflamamatory processes, are also frequently found in cases of human corneas that have lymphatic vessels. However, other findings such as lymphangiogenesis without the presence of angiogenesis, the presence of a greater amount of vessels in some cases and lymphangiogenesis without changes in its proximity remain in need of a better understanding.

Objetivo: Detectar a presença de vasos linfáticos na córnea através do exame histopatológico, buscando identificar os achados que são encontrados com maior frequência junto à presença desses vasos nesse tecido. Métodos: Estudo retrospectivo descritivo de botões corneanos humanos com linfangiogênese. Os tecidos foram provenientes de ceratoplastia penetrante no período compreendido entre os anos de 2006 e 2013. Foi realizada revisão de prontuários em busca de informações sobre sexo, idade e etiologia do transplante. Resultados: Foram incluídos 89 botões corneanos, sendo 37 de pacientes do sexo feminino e 52 do sexo masculino. A média das idades foi de 47,70 ± 23,95 anos (média ± DP). Linfangiogênese foi encontrada principalmente associada à hemangiogênese. Linfangiogênese isolada, no entanto, foi observada em 28 (31,46%) casos. Em 18 (20,22%) casos foram encontrados uma quantidade de vasos linfáticos cerca de quatro vezes maior que aquela encontrada na maioria das amostras. Em um grande número de casos foram encontrados condições inflamatórias como infecção e perfuração. Nas proximidades da linfangiogênese, encontramos muitos casos de sinéquia anterior e miofibroblastos. Em 17 (16,35%) casos nenhuma alteração foi evidenciada nas proximidades dos vasos linfáticos corneanos. Conclusão: Demonstramos, através do exame histopatológico, que achados reconhecidamente associados à linfangiogênese, como os processos inflamatórios, são encontrados também com frequência em casos de córneas humanas que possuem vasos linfáticos. Porém, outros achados evidenciados, como a linfangiogênese desacompanhada de angiogênese, a presença de uma maior quantidade de vasos em alguns casos e a linfangiogênese sem alterações em sua proximidade, permanecem necessitando de uma melhor compreensão.

Ursolic acid inhibits corneal graft rejection following orthotopic allograft transplantation in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of ursolic acid on corneal graft rejection in a rat model of othotopic corneal allograft transplantation.</p><p><b>METHODS</b>Forty-eight recipient Wistar rats were divided into normal control group with saline treatment (group A), autograft group with saline treatment (group B), SD rat allograft group with saline treatment (group C), and SD rat allograft group with intraperitoneal ursolic acid (UA) treatment group (group D). The rats received saline or UC (20 mg·kg(-1)·d(-1)) treatment for 12 days following othotopic graft transplantation. The grafts were evaluated using the Larkin corneal rejection rating system, and the graft survival was assessed with Kaplan-Meier analysis. On day 14, the grafts were harvested for histological examination, Western blotting, and assessment of expressions of interlukin-2 (IL-2), interferon-γ (IFN-γ), nuclear transcription factor-κB (NF-κB) p65, vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 (ICAM-1).</p><p><b>RESULTS</b>The allograft survival was significantly longer in group D than in group C (29.12±9.58 vs 9.67±2.16 days, P<0.05). UC treatment obviously reduced the expression levels of IL-2, IFN-γ, NF-κBp65, ICAM-1 and VEGF and increased inhibitory kappa B alpha (IκB-α) expression in the grafts, where no obvious inflammatory cell infiltration or corneal neovascularization was found.</p><p><b>CONCLUSION</b>As a NF-κB inhibitor, ursolic acid can prevent corneal neovascularization and corneal allograft rejection to promote graft survival in rats following orthotopic corneal allograft transplantation.</p>

Perspectivas farmacológicas de futuro en el tratamiento de la degeneración macular relacionada a la edad (DMRE) neovascular. Parte 2: terapia génica y fármacos en estudios pre clínicos / Pharmacological future perspectives in the treatment of age-related macular degeneration (AMD) neovascular. Part 2: gene therapy and drugs in pre-clinical trials

Objetivos: presentar una revisión acerca de la terapia génica y los fármacos en estudios preclínicos como nuevos y posibles blancos de tratamiento farmacológicos para la degeneración macular relacionada a la edad neovascular y el estado de los estudios clínicos de los mismos. Diseño del estudio: revisión de tema. Métodos: se realizó una búsqueda de la literatura electrónica disponible en EMBASE, PUBMED y Google Scholar acerca del tema y se complementa con la información encontrada en www.clinicaltrials.gov y la plataforma de registros internacionales de ensayos clínicos de la OMS. Conclusiones: la terapia génica vinculada a la degeneración macular asociada a la edad neovascular muestra un avance científico importante en el campo de la farmacología ocular pudiendo proporcionar eficacia tras una sola inyección de un vector que puede expresar continuamente una proteína elegida. Existen estudios pre-clínicos que sugieren nuevos y diversos blancos farmacológicos para la degeneración macular relacionada a la edad mostrando un perfil de seguridad y eficacia significativo.

Objectives: to review gene therapy and drugs in preclinical studies as potential new targets for pharmacological treatment for agerelated macular degeneration neovascular and the state of development clinical trials. Study design: literature review. Methods: a search of electronic literature available in EMBASE, PubMed and Google Scholar on the subject was performed and complemented with information found on www.clinicaltrials.gov and WHO platform of international clinical trials registers. Conclusions: the gene therapy linked to age-related macular degeneration shows a scientific important advance in the field of the ocular pharmacology being able to provide efficiency after a single injection of a vector that can express a chosen protein. There are preclinical studies that suggest new and different pharmacological targets for age-related macular degeneration showing a significant safety and efficacy profile.

A Two Case of 360 Degree Keratolimbal Allograft

PURPOSE: To report the clinical outcomes of 360-degree keratolimbal allograft in 2 patients. CASE SUMMARY: An 83-year-old female who had uncontrolled Mooren's ulcer invading 360 degrees of the limbus with corneal opacity received a 360-degree keratolimbal allograft (KLAL). Another 63-year-old female who had central corneal opacity and corneal neovascularization due to severe limbal cell deficiency with chemical injury received a 360-degree KLAL. During the average 17.5 months of follow-up, both eyes were tectonically maintained without severe graft rejection. CONCLUSIONS: A 360-degree KLAL may be an effective tectonic procedure for corneal opacity caused by limbal stem cell deficiency. Herein, we report 2 cases of successfully performed 360-degree KLAL with a literature review.

Efficacy of epigallocatechin gallate in treatment of alkali burn injury of murine cornea / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To evaluate the efficacy of epigallocatechin gallate (EGCG) in treatment of corneal alkali burn injury in mice.</p><p><b>METHODS</b>Corneal alkali burn injury was induced by sodium hydroxide method in C57BL/6J mice. The mice with cornea burns were treated intraperitoneally with EGCG solution or phosphate buffer solution (PBS) respectively. The healing of corneal epithelium, the formation of corneal neovascularization (CNV) and the inflammation reaction were assessed by slit -lamp microscopy and histological examination. Expression of vascular endothelial growth factor (VEGF) mRNA and protein in cornea was evaluated by real -time reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively. Myeloperoxidase (MPO) assay was used to quantitatively evaluate the polymorphonuclear neutrophils (PMNs) infiltration in the corneas.</p><p><b>RESULTS</b>The healing rate of corneal epithelium in EGCG group was significantly higher than that of PBS group at d1, d3 and d7 after treatment (d1: 41.0%±13.0% vs 23.8%±7.6%; d3: 76.6%±7.5% vs 61.2%±6.8%; d7: 87.8%±8.5% vs 74.0%±9.1%; all P <0.05). The CNV scores and the number of CNV in the corneal sections of EGCG group were significantly lower than those of PBS group at d3, d7 and d14 after treatment (CNV score: d3: 1.1±0.5 vs 6.6±1.0; d7: 1.3±0. 3 vs 8.1±1.0; d14: 0.9±0.2 vs 9.2±1.1; CNV number: d3: 1.68±0.61 vs 2.92±0.95; d7: 4.80±1.36 vs 7.92±1.28; d14: 3.64±0.71 vs 5.88±0.76; all P<0.05) . The expression of VEGF protein at d3 (0.19±0.05 vs 0.45±0.08) and d7 (0.42±0.07 vs 0.84±0.09), the expression of VEGF mRNA at d1, d3 and d7 in EGCG group were significantly lower than those in PBS group (all P <0.05). Compared to PBS group, the inflammatory index at d3 (3.2±0.4 vs 3.7±0.5) and d7 (2.3±0.5 vs 4.0±0.0), the number of PMNs in the corneal sections and the MPO values at d3, d7 and d14 in EGCG group were significantly decreased (PMNs: d3: 34.5±15.7 vs 90.0±28.8; d7: 17.1±11.4 vs 54.9±25.9; d14: 12. 8±4.6 vs 39.0±17.9; all P <0.05).</p><p><b>CONCLUSION</b>In the murine corneal alkali burn model, intraperitoneal injection of EGCG solution can promote the healing of corneal epithelium, inhibit the formation of CNV and reduce the inflammatory cell infiltration in the corneas.</p>

Comparison of the effects of subconjunctival and topical anti-VEGF therapy (bevacizumab) on experimental corneal neovascularization / Comparação do efeito da terapia anti-VEGF (bevacizumab) subconjuntival e tópica na neovascularização corneana experimental

Purpose: To compare the effects of bevacizumab applied either subconjunctivally or topically, in a rat model of corneal neovascularization induced by alkali burn. Methods: The right corneas of 24 Wistar-Albino rats were cauterized with silver nitrate sticks. The rats were divided randomly and equally into three groups: no treatment control (n=8), subconjunctival bevacizumab treatment (n=8), and topical bevacizumab treatment (n=8). Immediately following cauterization, the subconjunctival group was treated with a 0.05 ml (1.25 mg) bevacizumab subconjunctival injection. The topical group was treated with 10 mg/ml bevacizumab twice daily, and the control group received subconjunctival saline injections twice daily. The burn stimulus and neovascularization scores were evaluated using a technique previously described by Mahoney and Waterbury. Digital photographs were obtained before the eyes were enucleated and corneal sections were then analyzed by histopathology. Results: The mean burn stimulus score was 1.86 ± 0.6 and there was no statistical difference between the groups (p=0.730). The mean neovascularization scores in the subconjunctival and topical bevacizumab groups were statistically lower than the control group (p<0.05). The mean percentage area of corneal neovascularization was 82.5 ± 22.1 in the control group, 42.7 ± 15.0 in the subconjunctival group, and 55.8 ± 18.2 in the topical group. The differences between the control and treatment groups were statistically significant (p<0.05). Histopathology showed that the treatment groups presented less neovascularization, inflammation, and fibroblast activity than the control group (p<0.05). Conclusions: This study demonstrates that both subconjunctival and topical administrations of bevacizumab inhibit corneal neovascularization and decrease inflammation and fibroblast activity in a rat model of corneal neovascularization induced by alkali burn. .

Objetivo: Comparar o efeito de bevacizumab aplicado subconjuntival e topicamente em um modelo de neovascularização de córnea de ratos induzida por queimadura alcalina. Métodos: Córneas direitas de 24 ratos Wistar-Albino foram cauterizados por nitrato de prata. Os indivíduos foram divididos aleatoriamente e igualmente em três grupos: controle (n=8), o bevacizumab subconjuntival (n=8), o bevacizumab tópico (n=8). Imediatamente após a cauterização, 0,05 ml (1,25 mg) de bevacizumab foi injetado no grupo subconjuntival. Grupo tópico foi inculcado com 10 mg/ml de bevacizumab duas vezes por dia. O grupo controle recebeu solução salina normal, topicamente, duas vezes ao dia. A graduação do estímulo da queimadura e a graduação da neovascularização foram avaliados utilizando a técnica descrita por Mahoney e Waterbury. Fotografias digitais foram obtidas dos olhos serem enucleados. Seções da córnea foram analisadas por histopatologia. Resultados: A média da graduação do estímulo da queimadura foi de 1,86 ± 0,6 e não houve diferença estatisticamente entre os grupos (p=0,730). As médias das graduações da neovascularização no grupo bevacizumab subconjuntival e no grupo bevacizumab tópico foram estatisticamente menores do que o grupo controle (p<0,05). A percentagem média de área de neovascularização da córnea foi de 82,5 ± 22,1 no grupo controle, 42,7 ± 15,0 no grupo subconjuntival e 55,8 ± 18,2 no grupo tópico. As diferenças entre os grupos de tratamento e grupo de controlo foram estatisticamente significativos (p<0,05). A histopatologia mostrou que os grupos de tratamento apresentavam menos neovascularização, inflamação e atividade de fibroblastos do que o grupo controle (p<0,05). ...

Bevacizumab subconjuntival y su efectividad en la regresión de la neovascularización corneal evaluado mediante angiografía fluoresceínica de segmento anterior / Subconjunctival bevacizumab effectiveness in corneal neovascularization regression evaluated with anterior segment fluorescein angiography

Objetivo: evaluar objetivamente mediante el uso de angiografía de segmento anterior la reducción del grado de neovascularización corneal con la aplicación de bevacizumab subconjuntival. Diseño: serie de casos con intervención. Metodología: nueve ojos con neovascularización corneal estromal secundaria a diferentes condiciones se sometieron a la realización de angiografía fluoresceínica de segmento anterior; cuatro semanas después se aplicaron 3 dosis de bevacizumab subconjuntival limbar de 2,5 mg/0,1cc cada una sobre el cuadrante comprometido con un intervalo de un mes entre cada aplicación. Cuatro semanas después se realizó una nueva angiografía. Las fotos pre-aplicación y post aplicación fueron analizadas por 3 evaluadores. Se definió como mejoría si había una mejoría ≥30%, basado en una escala de mejoría de 0 a 10. Resultados: se encontró un alto rango de variabilidad en la regresión de la neovascularización corneal (entre 3% y 92%) con un promedio de mejoría del 41% y posibilidad de falla de 44,4% independientemente de su etiología. Se obtuvieron pobres resultados en presencia de cuerpos extraños en córnea (segmentos intraestromales o suturas corneales) con una mejoría entre 3% y 7%. Pacientes sin cuerpo extraño en córnea obtuvieron una mejoría promedio de la neovascuarización corneal del 70%. No hubo efectos secundarios sistémicos o locales. Conclusion: el uso del bevacizumab subconjuntival como terapia antiangiogénica es una alternativa con buena tasa de efectividad en pacientes con neovascularización corneal sin presencia de cuerpos extraños corneales.

Purpose: to assess corneal stromal neovascularization accurately and its improvement by using anterior segment fluorescein angiography imaging after subconjunctival bevacizumab injection. Design: interventional case series. Methodology: an anterior segment fluorescein angiography was performed in nine eyes with stromal neovascularization secondary to different etiologies. Patients underwent subconjunctival bevacizumab injections, each one receiving three injections containing 2,5mg/0,1ml bevacizumab each, at monthly intervals. Four weeks after the last injection was applied, a new anterior segment fluorescein angiography was done; pre and post-treatment angiographies were analyzed by three ophthalmologists. A favorable outcome was defined as an improvement of 30% in corneal neovascularization based on a previously established score from 0 to 10. Results: findings were variable, with corneal neovascularization improving between 3% and 92% (mean improvement 41%) for all eyes included, and a 44,4% chance of failure. Poor results were obtained from eyes that had some type of intracorneal foreign body such as intracorneal ring segments (ICRS) and corneal sutures with an improvement range from 3% to 7% whereas eyes with no foreign bodies had a mean reduction in corneal neovascularization of 70%. No side effects were reported. Conclusions: subconjunctival Bevacizumab use as antiangiogenic therapy is an alternative with a high success rate in patients without intracorneal foreign bodies, although it is clearly not as effective in patients with foreing body-induced neovascularization.

Biometric Risk Factors for Corneal Neovascularization Associated with Hydrogel Soft Contact Lens Wear in Korean Myopic Patients

PURPOSE: To investigate the biometric risk factors for corneal surface complications associated with hydrogel soft contact lens (SCL) fitting in myopic patients in Korea. METHODS: This is a retrospective case-control study. The records of 124 subjects (124 eyes) who wore SCLs on a daily basis were reviewed. Thirty-one patients (31 eyes) who were diagnosed with corneal neovascularization (NV) while wearing SCLs were included in the complication group. Ninety-three age- and sex-matched patients (93 eyes) who wore SCLs, who did not have corneal NV and who visited our clinic for correction of refractive errors were included in the control group. The degree of spherical equivalent, astigmatism and corneal base curve radius (BCR) were compared in both groups. RESULTS: Patients with NV exhibited poorer best corrected visual acuity and more myopia than controls (p = 0.008 and 0.006, respectively). In univariate analysis, highly myopic patients (-9 diopters [D] or higher) were more likely to experience NV (odds ratio [OR], 2.232; 95% confidence interval [CI], 1.602 to 3.105). High astigmatism (> or =2 D) increased the risk of complications (OR, 2.717; 95% CI, 1.141 to 6.451). Steep cornea, in which BCR was <7.5 mm, also raised the risk of complications (OR, 4.000; 95% CI, 1.661 to 9.804). Flat cornea was not a risk factor for the development of NV. CONCLUSIONS: High myopia, high astigmatism, and steep cornea seemed to be risk factors in the development of corneal NV in SCL wearers.

A Case of Corneal Opacity Improved by Treatment of Demodex Blepharitis

PURPOSE: To report a case of corneal opacity improved by treatment of demodex blepharitis. CASE SUMMARY: A 50-year-old female who received sub-laser-assisted in situ keratomileusis (LASIK) flap surgery was referred to our clinic with corneal opacity and neovascularization in her left eye. Her visual acuity was 0.5. Telangiectasis of the eyelid margin and meibomian gland dysfunction were observed. Seven Demodex folliculorum were found in 4 eyelashes of the left eye. Lid scrub with 0.4% polyhexamethylene biguanide (PHMB) and ointment containing dexamethasone was started for demodex blepharitis treatment. After 6 months of treatment, the number of Demodex folliculorum was decreased to 2 and the best corrected visual acuity was 0.8. Corneal opacity and neovascularization were also improved. CONCLUSIONS: The present study showed that demodex blepharitis can induce atypical corneal opacity and neovascularization after LASIK surgery. Evaluation and treatment of demodex blepharitis in these patients is important.

Ranibizumab Injection for Corneal Neovascularization Refractory to Bevacizumab Treatment

Vascular endothelial growth factor inhibitor is an emerging therapeutic modality for various ocular diseases with neovascularization (NV). However, for corneal NV, controversy remains regarding whether bevacizumab or ranibizumab is superior. A 32-year-old female diagnosed with herpetic keratoconjunctivitis with refractory corneal NV despite two previous subconjunctival and intrastromal bevacizumab injections, received two subconjunctival and intrastromal ranibizumab injections. Six months postoperatively, there was significant regression of the neovascular area and vessel caliber. Here, the authors report a case of improvement in corneal NV with subconjunctival and intrastromal ranibizumab injections, which was previously refractory to bevacizumab injection. The findings may suggest a new prospect in treating corneal NV.