Javier Araiz

Beneficial Effect of Docosahexanoic Acid and Lutein on Retinal Structural, Metabolic, and Functional Abnormalities in Diabetic Rats

Purpose: To assess the effect of docosahexanoic acid (DHA) and lutein (both compounds with anti-inflammatory and antioxidant properties) on experimental diabetic retinopathy. Methods: Male Wistar rats were studied: non-diabetic controls, untreated diabetic controls, and diabetic rats were treated with DHA and lutein or the combination of DHA + insulin and lutein + insulin for 12 weeks. Oxidative stress and inflammatory markers, apoptosis, and functional tests were studied to confirm biochemical and functional changes in the retina of diabetic rats. Malondialdehyde (MDA), glutathione concentrations (GSH), and glutathione peroxidase activity (GPx) were measured as oxidative stress markers. TUNEL assay and caspase-3 immunohistochemistry and electroretinogram were performed. Results: Diabetes increases oxidative stress, nitrotyrosine concentrations, and apoptosis in the retina. At 12 weeks after onset of diabetes, total thickness of retinas of diabetic rats was significantly less than that in control rats. Specifically, the thickness of the outer and inner nuclear layers was reduced significantly in diabetic rats and demonstrated a loss of cells in the GCL. These retinal changes were avoided by the administration of insulin and DHA and lutein alone or in combination with insulin. Impairment of the electroretinogram (b-wave amplitude and latency time) was observed in diabetic rats. DHA and lutein prevented all these changes even under hyperglycemic conditions. Conclusions: Lutein and DHA are capable of normalizing all the diabetes-induced biochemical, histological, and functional modifications. Specifically, the cell death mechanisms involved deserve further studies to allow the proposal as potential adjuvant therapies to help prevent vision loss in diabetic patients.

Twelve-month outcome after one intravitreal injection of bevacizumab to treat myopic choroidal neovascularization.

Purpose: To report the changes during a 1-year follow-up in visual acuity and macular thickness in a series of highly myopic eyes with choroidal neovascularization treated with bevacizumab. Methods: Retrospective and multicenter study including 107 highly myopic eyes from 107 patients (mean age, 55 years) with subfoveal or juxtafoveal choroidal neovascularization. All cases were treated by one intravitreous injection of 1.25 mg bevacizumab. Best-corrected visual acuity and macular thickness with the optical coherence tomography were evaluated at baseline and then monthly during 1 year. Results: Logarithm of the minimum angle of resolution best-corrected visual acuity at baseline averaged 0.72 (standard deviation [SD], 0.43) versus 0.53 (SD, 0.41) at 1 year after treatment (P < 0.001). Logarithm of the minimum angle of resolution best-corrected visual acuity was 0.30 or better in 49 of 107 eyes (45%) at 1 year. Thirty-three eyes (30%) gained at least 3 Early Treatment Diabetic Retinopathy Study lines (15 letters) during the follow-up. In 43 eyes (40%), reinjections were necessary because signs of choroidal neovascularization activity were still evident. The mean number of reinjections was 0.8 (SD, 1.3). Best-corrected visual acuity improvement was better in the younger group (younger than 50 years). No adverse reactions were reported. Conclusion: One intravitreal bevacizumab injection seems to be an effective therapeutic approach to treat choroidal neovascularization in highly myopic eyes. Careful monitoring is necessary to assess the need for reinjections.

Silicone oil as a delivery vehicle for BCNU in rabbit proliferative vitreoretinopathy.

The antiproliferative properties of a single intravitreous injection of BCNU [carmustine; 1,3-bis(2 chloroethyl)-1-nitrosourea] dissolved in 1 ml of medical grade, 1,000-centistoke silicone oil were evaluated in a rabbit model of proliferative vitreoretinopathy (PVR). 10 µg and 15 µg of BCNU in 1 ml silicone oil resulted in a 46% and 27% reduction in the incidence of retinal detachments, respectively. Chi-square tests showed a significant statistical difference (P < 0.05) between the control and treated groups. However, histopathologic examination of the eyes injected with BCNU and silicone oil indicated some retinal disorganization even at the lower therapeutic levels. With a therapeutic index of <1.0, BCNU in silicone oil has a low margin of safety for treatment of PVR. Nevertheless, this study demonstrates that silicone oil when used for retinal tamponade in PVR may be the vehicle for delivery of a lipophilic antiproliferative agent.

INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR CHOROIDAL NEOVASCULARIZATION SECONDARY TO PATHOLOGIC MYOPIA: SIX YEARS OUTCOME.

Purpose: To report the visual outcome after 6-year follow-up in highly myopic eyes with choroidal neovascularization treated with anti-vascular endothelial growth factor drugs. Methods: Retrospective, nonrandomized, multicenter, consecutive, and interventional case series. Results: Seventy-eight patients were treated with intravitreal bevacizumab and 19 with ranibizumab. Mean age of the patients was 56.5 years (SD, 13.3). The average number of letters read was 56.7 (SD, 19.0) at baseline; 65.7 (SD, 18.4) at 12 months; 63.6 (SD, 20.6) at 24 months; 62.4 (SD, 21.4) at 36 months; 60.6 (SD, 22.0) at 48 months; 58.9 (SD, 22.9) at 60 months, and 58.4 (SD, 22.7) at 72 months (P < 0.01, between initial vs. 12, 24, and 36 months; P = 0.07, 0.3, and 0.5 between initial vs. 48, 60, and 72 months, respectively; Students t-test paired data). The mean total number of intravitreal injections was 3.3 (SD, 2.3; range, 1–9). Conclusion: Bevacizumab and ranibizumab are effective therapies and show similar clinical effects in myopic eyes with choroidal neovascularization. Visual acuity gain is maintained at a 3-year follow-up. The improvement is no longer statistically significant at Years 4, 5, and 6.

Do Nutritional Supplements Have a Role in Age Macular Degeneration Prevention

Purpose. To review the proposed pathogenic mechanisms of age macular degeneration (AMD), as well as the role of antioxidants (AOX) and omega-3 fatty acids (ω-3) supplements in AMD prevention. Materials and Methods. Current knowledge on the cellular/molecular mechanisms of AMD and the epidemiologic/experimental studies on the effects of AOX and ω-3 were addressed all together with the scientific evidence and the personal opinion of professionals involved in the Retina Group of the OFTARED (Spain). Results. High dietary intakes of ω-3 and macular pigments lutein/zeaxanthin are associated with lower risk of prevalence and incidence in AMD. The Age-Related Eye Disease study (AREDS) showed a beneficial effect of high doses of vitamins C, E, beta-carotene, and zinc/copper in reducing the rate of progression to advanced AMD in patients with intermediate AMD or with one-sided late AMD. The AREDS-2 study has shown that lutein and zeaxanthin may substitute beta-carotene because of its potential relationship with increased lung cancer incidence. Conclusion. Research has proved that elder people with poor diets, especially with low AOX and ω-3 micronutrients intake and subsequently having low plasmatic levels, are more prone to developing AMD. Micronutrient supplementation enhances antioxidant defense and healthy eyes and might prevent/retard/modify AMD.

Three versus one intravitreal bevacizumab injections as initial protocol to treat myopic choroidal neovascularization

(Fig. 1E). Using FISH analysis, we found no 13q14 deletion (site of the retinoblastoma gene) in the atypical cells. However, lacked 13q14 deletion does not exclude retinoblastoma, as only 5–10% of hereditary retinoblastomas reveal deletion in the 13q14 RB1 locus (Kivelä et al. 2003). The low proliferation rate (Kim et al. 1999; Schwimer & Prayson 2001), the GFAP-positivity of the cells (He et al. 1992), and the negative FISH analysis of 13q14 did not support a retinoblastoma diagnosis but pointed towards retinal dysplasia like Norrie’s disease. DNA analysis of the child and his mother was performed in regard to the NDP gene, which upon mutation is responsible for Norrie’s disease, ROP, or X-linked familial exudative vitreoretinopathy (Berger et al. 1992; Wu et al. 2007). The NDP gene was evaluated for mutations by PCR amplification of all three exons and all four exon–intron boundaries followed by direct sequencing. The DNA analysis revealed a mutation in the first codon of the Norrin gene (c.1A > G and p.M1V genes) which because of the localization of the NDP gene on the X chromosome caused hemizygous situation in the child. Further DNA analysis confirmed the mother to be a carrier of the same sequence variant c.1A > G (p.M1V). Thus, all results taken together were consistent with X-linked Norrie’s disease. In conclusion, based on our results, in cases of dysplastic retinas with bilateral multiple unclear pseudotumourous lesions, cytology seems to be a useful tool to differentiate in a very short term patients with Norrie’s syndrome from those with retinoblastoma or lymphoma. However, retinoblastomas frequently harbour infiltrated retinal elements that may cause confusion or misdiagnosis if only small tumour portions are available for assessment. Also, an eye with suspected retinoblastoma should not be vitrectomized or biopsied, so as not to spread tumour cells extrasclerally.

Spectral-domain optical coherence tomography study of macular structure as prognostic and determining factor for macular hole surgery outcome

Purpose: To evaluate postoperative spectral-domain optical coherence tomography findings after macular hole surgery. Methods: Retrospective, interventional, nonrandomized study. Overall, 164 eyes of 157 patients diagnosed with macular hole were operated on by vitrectomy and internal limiting membrane peeling. Preoperative and postoperative best-corrected visual acuity and spectral-domain optical coherence tomography images were obtained. Two groups were considered on the basis of the postoperative integrity of the back reflection line from the ellipsoid portion of the photoreceptor inner segment: group A (disruption of ellipsoid portion of the inner segment line, 60 eyes) and group B (restoration of ellipsoid portion of the inner segment line, 104 eyes). Results: Logarithm of the minimum angle of resolution best-corrected visual acuity improved significantly after the surgery of macular hole from a mean preoperative value of 0.79 ± 0.37 (range, 0.15–2.00) to a mean postoperative value of 0.35 ± 0.31 (range, 0.00–1.30) at the last follow-up visit (P < 0.01). Best-corrected visual acuity improved significantly in the 2 groups analyzed (all P < 0.01). A larger improvement was found in group B than in group A (P < 0.01). Conclusion: Ellipsoid portion of the inner segment line reconstruction seems to be a good prognostic factor for visual rehabilitation after macular hole surgery.

Comparación de tres métodos de inducción del incremento crónico de la presión intraocular en el cerdo (glaucoma experimental)

espanolObjetivo: Comparar tres metodos de induccion de glaucoma experimental en el cerdo adulto, basados en el aumento cronico de la presion intraocular (PIO). Material y metodos: En el presente estudio se emplearon un total de 16 cerdos adultos. En todos los casos se utilizaron los ojos derechos como control y los ojos izquierdos fueron operados. Dividimos los animales en tres grupos: 1) tres cerdos a los que se les cauterizo tres de las venas epiesclerales (periodo de seguimiento = 21 semanas), 2) seis animales a los que se les inyecto una solucion que contenia fluoroesferas en la camara anterior (periodo de seguimiento = 11 semanas) y 3) cuatro cerdos a los que se les inyecto una solucion que contenia fluoroesferas junto con metil-celulosa en la camara anterior (periodo de seguimiento = 11 semanas). Resultados: La cauterizacion de las venas epiesclerales resulto ser el unico de los metodos que produjo un aumento mantenido de la PIO a lo largo de la mayor parte del periodo experimental. Ademas, el aumento de la PIO producido siguiendo este metodo resulto en una perdida selectiva de celulas ganglionares de la retina (CGR), la cual afecto principalmente a la retina media y periferica y causo un aumento en el area media de las CGR supervivientes. Conclusiones: La cauterizacion de las venas epiesclerales provoco un aumento mantenido y significativo de la PIO asi como una perdida de CGR, en comparacion con los otros dos metodos utilizados en el presente estudio, los cuales apenas modificaron la distribucion de las CGR de cerdo. Por tanto, concluimos que la cauterizacion de las venas epiesclerales es el mejor de los metodos ensayados para inducir glaucoma experimental en cerdo. EnglishPurpose: To compare three methods of inducing experimental glaucoma in the adult pig, based on achieving chronic elevation of the intraocular pressure (IOP). Methods: A total of 16 adult pigs were used in the present study. In all instances, the right eye was used as control and the left eye as the experimental eye. The animals were divided into three groups: 1) 3 pigs in which 3 episcleral veins were cauterized (experimental period = 21 weeks); 2) 6 animals in which the anterior chamber of the eye was injected with a solution containing latex fluorospheres (experimental period = 11 weeks); and 3) 4 pigs in which the anterior chamber of the eye was injected with a solution containing latex fluorospheres plus methylcellulose (experimental period = 11 weeks). Results: The episcleral vein cauterization was the only method which produced a sustained elevation of the IOP throughout most of the experimental period. Moreover, the elevation of the IOP achieved by this method resulted in selective retinal ganglion cell (RGC) loss that affected mainly the mid-peripheral and peripheral retina and caused an increase in the mean soma area of the remaining RGCs. Conclusions: Cauterization of the episcleral veins resulted in a significant and sustained elevation of the IOP and RGC loss when compared with the other two approaches tested in the present study, which barely modified the pigs RGC distribution. Thus, we conclude that the episcleral vein cauterization is the best of the methods tested to induce experimental glaucoma in the pig.

A delphi study to detect deficiencies and propose actions in real life treatment of neovascular age-related macular degeneration.

Purpose. Spanish retina specialists were surveyed in order to propose actions to decrease deficiencies in real-life neovascular age macular degeneration treatment (nv-AMD). Methods. One hundred experts, members of the Spanish Vitreoretinal Society (SERV), were invited to complete an online survey of 52 statements about nv-AMD management with a modified Delphi methodology. Four rounds were performed using a 5-point Linkert scale. Recommendations were developed after analyzing the differences between the results and the SERV guidelines recommendations. Results. Eighty-seven specialists completed all the Delphi rounds. Once major potential deficiencies in real-life nv-AMD treatment were identified, 15 recommendations were developed with a high level of agreement. Consensus statements to reduce the burden of the disease included the use of treat and extend regimen and to reduce the amount of diagnostic tests during the loading phase and training technical staff to perform these tests and reduce the time between relapse detection and reinjection, as well as establishing patient referral protocols to outside general ophthalmology clinics. Conclusion. The level of agreement with the final recommendations for nv-AMD treatment among Spanish retinal specialist was high indicating that some actions could be applied in order to reduce the deficiencies in real-life nv-AMD treatment.

Individualized Therapy with Ranibizumab in Wet Age-Related Macular Degeneration

Individualized treatment regimens may reduce patient burden with satisfactory patient outcomes in neovascular age-related macular degeneration. Intravitreal anti-VEGF drugs are the current gold standard. Fixed monthly injections offer the best visual outcome but this regimen is not commonly followed outside clinical trials. A PRN regimen requires monthly visits where the patient is treated in the presence of signs of lesion activity. Therefore, an early detection of reactivation of the disease with immediate retreatment is crucial to prevent visual acuity loss. Several trials suggest that “treat and extend” and other proactive regimens provide a reasonable approach. The rationale of the proactive regimens is to perform treatment anticipating relapses or recurrences and therefore avoid drops in vision while individualizing patient followup. Treat and extend study results in significant direct medical cost savings from fewer treatments and office visits compared to monthly treatment. Current data suggest that, for one year, PRN is less expensive, but treat and extend regimen would likely be less expensive for subsequent years. Once a patient is not a candidate to continue with treatment, he/she should be sent to an outpatient unit with adequate resources to follow nAMD patients in order to reduce the burden of specialized ophthalmologist services.