Recovery course of foveal microstructure in the nonsurgical resolution of full-thickness macular hole.

PURPOSE: To analyze the recovery course of foveal microstructures in eyes with nonsurgical healing of full-thickness macular hole (FTMH). METHODS: By serial OCT scans, the temporal healing sequences were analyzed in ocular trauma, vitreomacular traction (VMT), cystoid macular edema (CME), and the remaining group. We evaluated correlations between the final best-corrected spectacle visual acuity and reconstruction time of external limiting membrane (ELM), and inner segment/outer segment (IS/OS). RESULTS: The healing (mean±standard deviation in months) most involved fusion at the level of the outer nuclear layer (ONL) (6.3±10.5) followed by restoration of ELM (9.1±13.8), and lastly, by IS/OS regeneration (13.1±19.5). In severe blunt ocular trauma, healing was fast and involved subretinal zipper glue-like reapposition with resulting outer retinal atrophy. Best spectacle-corrected visual acuity correlated with normalization of the clivus (p=0.012), faster ELM (p=0.006), and IS/OS reconstitution (p=0.024). Recurrence of FTMH occurred when the healing was halted (3 eyes) or was aberrant by lamellar hole epiretinal proliferation (LHEP) (3 eyes) or by the persistence of VMT (1 eye). CONCLUSION: Recovery sequences proceeded from the ONL to the deeper layers with BCVA correlating absolutely and temporally with the restoration of outer retinal layer integrity.

CNNs for automatic glaucoma assessment using fundus images: an extensive validation.

BACKGROUND: Most current algorithms for automatic glaucoma assessment using fundus images rely on handcrafted features based on segmentation, which are affected by the performance of the chosen segmentation method and the extracted features. Among other characteristics, convolutional neural networks (CNNs) are known because of their ability to learn highly discriminative features from raw pixel intensities. METHODS: In this paper, we employed five different ImageNet-trained models (VGG16, VGG19, InceptionV3, ResNet50 and Xception) for automatic glaucoma assessment using fundus images. Results from an extensive validation using cross-validation and cross-testing strategies were compared with previous works in the literature. RESULTS: Using five public databases (1707 images), an average AUC of 0.9605 with a 95% confidence interval of 95.92-97.07%, an average specificity of 0.8580 and an average sensitivity of 0.9346 were obtained after using the Xception architecture, significantly improving the performance of other state-of-the-art works. Moreover, a new clinical database, ACRIMA, has been made publicly available, containing 705 labelled images. It is composed of 396 glaucomatous images and 309 normal images, which means, the largest public database for glaucoma diagnosis. The high specificity and sensitivity obtained from the proposed approach are supported by an extensive validation using not only the cross-validation strategy but also the cross-testing validation on, to the best of the authors' knowledge, all publicly available glaucoma-labelled databases. CONCLUSIONS: These results suggest that using ImageNet-trained models is a robust alternative for automatic glaucoma screening system. All images, CNN weights and software used to fine-tune and test the five CNNs are publicly available, which could be used as a testbed for further comparisons.

Electrophysiological and clinical tests in dry age-related macular degeneration follow-up: differences between mfERG and OCT.

BACKGROUND: Age-related macular degeneration (AMD) is one of the major causes of progressive and debilitating visual impairment in developed countries and has become a growing health and social issue that needs to be addressed. Imaging techniques and functional tests are useful to assess the degree of macular dysfunction and AMD progression. However, given the slow progression of the disease, it is necessary to identify which techniques are more sensitive for the diagnosis and monitoring of patients with AMD. PURPOSE: To study changes observed with both imaging techniques and electrophysiological tests in dry AMD-diagnosed patients during 2 years in order to identify the most sensitive technique. METHODS: Fundus photography, OCT (macular thickness and number of drusen), Pattern VEP (P100 wave), Pattern ERG (P50 wave) and multifocal ERG (central rings) were carried out in 30 patients that were diagnosed with dry AMD in both eyes. The tests were repeated 1 and 2 years later. RESULTS: No statistically significant changes were observed in visual acuity or in the severity of the disease throughout the study. OCT showed an increase in the number of drusen, as well as in macular thickness. As for the electrophysiological techniques, no significant changes were observed throughout the study in Pattern VEP or Pattern ERG. mfERG showed significant alterations. Statistical analysis showed that mfERG is more efficient in detecting changes throughout the experimental period. CONCLUSIONS: OCT and mfERG are useful in the diagnosis and monitoring of dry AMD patients, whilst mfERG is the most sensitive technique to study the progression of this disease in short periods of time.

A rapid method for measuring intraocular lens power in vitro with a focimeter.

In this paper we describe a new method for measuring the intraocular lens (IOL) power using a focimeter, a negative ophthalmic lens and a saline solution (0.9% NaCl). To test this we measured the power of 58 different IOLs and we compared them with the power stated by the manufacturer. Despite the limitations, the results show a good correlation.

Image quality comparison of two multifocal IOLs: influence of the pupil.

PURPOSE: To evaluate the effect of pupil size on image quality of a sectorial multifocal intraocular lens (IOL), the Lentis Mplus (Oculentis GmbH, Berlin, Germany), and the Acri.LISA IOL (Carl Zeiss Meditec, Jena, Germany). METHODS: The authors measured the MTFs of the Lentis Mplus LS-312 IOL and the Acri.LISA 366D IOL with three different sizes of pupil diameters: 3, 4, and 5 mm. The MTF was calculated from the cross-line spread function recorded with the OPAL Vector System (Image Science Ltd., Oxford, UK) by using fast Fourier-transform techniques. RESULTS: In distance focus, the image quality provided by the Lentis Mplus IOL was better than that of the Acri. LISA IOL with all pupil diameters. In near focus, the MTF of the Acri.LISA IOL was better with a 3-mm pupil, but poor with larger pupils. The aberration effect was equal in both IOLs in distance focus, but in near focus and with a 3-mm pupil, the Acri.LISA IOL was less affected by the aberration than the Lentis Mplus IOL. CONCLUSION: The Lentis Mplus IOL provides better distance image quality than the Acri.LISA IOL, whereas the near image quality of the Acri.LISA IOL is better with small-pupil diameter. The sectorial design makes this IOL more suitable for patients with a pupil diameter greater than 3 mm.

Macrophages and Uveitis in Experimental Animal Models.

Resident and infiltrated macrophages play relevant roles in uveitis as effectors of innate immunity and inductors of acquired immunity. They are major effectors of tissue damage in uveitis and are also considered to be potent antigen-presenting cells. In the last few years, experimental animal models of uveitis have enabled us to enhance our understanding of the leading role of macrophages in eye inflammation processes, including macrophage polarization in experimental autoimmune uveoretinitis and the major role of Toll-like receptor 4 in endotoxin-induced uveitis. This improved knowledge should guide advantageous iterative research to establish mechanisms and possible therapeutic targets for human uveitis resolution.

New Immunosuppressive Therapies in Uveitis Treatment.

Uveitis is an inflammatory process that initially starts in the uvea, but can also affect other adjacent eye structures, and is currently the fourth cause of blindness in developed countries. Corticoids are probably the most widespread treatment, but resorting to other immunosuppressive treatments is a frequent practice. Since the implication of different cytokines in uveitis has been well demonstrated, the majority of recent treatments for this disease include inhibitors or antibodies against these. Nevertheless, adequate treatment for each uveitis type entails a difficult therapeutic decision as no clear recommendations are found in the literature, despite the few protocolized clinical assays and many case-control studies done. This review aims to present, in order, the mechanisms and main indications of the most modern immunosuppressive drugs against cytokines.

Glutathione and a Pool of Metabolites Partly Related to Oxidative Stress Are Associated with Low and High Myopia in an Altered Bioenergetic Environment.

Oxidative stress forms part of the molecular basis contributing to the development and manifestation of myopia, a refractive error with associated pathology that is increasingly prevalent worldwide and that subsequently leads to an upsurge in degenerative visual impairment due to conditions that are especially associated with high myopia. The purpose of our study was to examine the interrelation of potential oxidative-stress-related metabolites found in the aqueous humor of high-myopic, low-myopic, and non-myopic patients within a clinical study. We conducted a cross-sectional study, selecting two sets of patients undergoing cataract surgery. The first set, which was used to analyze metabolites through an NMR assay, comprised 116 patients. A total of 59 metabolites were assigned and quantified. The PLS-DA score plot clearly showed a separation with minimal overlap between the HM and control samples. The PLS-DA model allowed us to determine 31 major metabolite differences in the aqueous humor of the study groups. Complementary statistical analysis of the data allowed us to determine six metabolites that presented significant differences among the experimental groups (p < 005). A significant number of these metabolites were discovered to have a direct or indirect connection to oxidative stress linked with conditions of myopic eyes. Notably, we identified metabolites associated with bioenergetic pathways and metabolites that have undergone methylation, along with choline and its derivatives. The second set consisted of 73 patients who underwent a glutathione assay. Here, we showed significant variations in both reduced and oxidized glutathione in aqueous humor among all patient groups (p < 0.01) for the first time. Axial length, refractive status, and complete ophthalmologic examination were also recorded, and interrelations among metabolic and clinical parameters were evaluated.

External validation of existing formulas to predict the risk of developing proliferative vitreoretinopathy: the Retina 1 Project; report 5.

PURPOSE: To externally validate the accuracy of previously published formulas for predicting proliferative vitreoretinopathy development after retinal detachment surgery. METHODS: Clinical variables from consecutive retinal detachment patients (n = 1,047) were collected from the Retina 1 Project conducted in 17 Spanish and Portuguese centers. These data were used for external validation of four previously published formulas, F1 to F4. Receiver-operating characteristic curves were used to validate the quality of formulas, and measures of discrimination, precision, and calibration were calculated for each. Concordance among the formulas was determined by Cohen kappa index. RESULTS: The areas under the receiver-operating characteristic curves were as follows: F1, 0.5809; F2, 0.5398; F3, 0.5964; and F4, 0.4617. F1 had the highest accuracy, 74.21%. Almost 19% of proliferative vitreoretinopathy cases were correctly classified by F1 compared with 13%, 15%, and 10% for F2, F3, and F4, respectively. There was moderate concordance between F2 and F3 but little between the other formulas. CONCLUSION: After external validation, none of the formulas were accurate enough for routine clinical use. To increase its usefulness, other factors besides the clinical ones considered here should be incorporated into future formulas for predicting risk of developing proliferative vitreoretinopathy.

Recovery course of persistent posterior subretinal fluid after successful repair of rhegmatogenous retinal detachment.

PURPOSE: To investigate best corrected visual acuity (BCVA), subretinal fluid (SRF) absorption time or ellipsoid zone (EZ) restoration time and various variables in patients with persistent SRF after successful primary repair of rhegmatogenous retinal detachment (RRD). METHODS: This retrospective multicenter study allowed independent analysis of the healing pattern by two observers based on composite of serial cross-sectional macular optical coherence tomography (OCT) scans. Univariate and multivariate analyses were implemented. RESULTS: One hundred and three cases had persistent SRF after pars plana vitrectomy, scleral buckling, or pneumatic retinopexy. By univariate analysis, SRF resolution time correlated positively with the number of retinal breaks (p < 0.001) and with increased myopia (p = 0.011). Using multivariate analysis, final BCVA (log MAR) correlated positively with age, duration of RRD, initial BCVA (OR = 3.28; [95%CI = 1.44-7.47]; p = 0.015), and SRF resolution time (OR = 0.46 [95%CI 0.21-1.05]; p = 0.049). EZ restoration time was longer with increasing number of retinal tears (OR = 0.67; [95%CI 0.29-1.52]; p = 0.030), worse final BCVA, and presence of macula-off RRD (OR = 0.26; [95%CI 0.08-0.88]; p = 0.056). SRF resolution time correlated marginally with prone position. CONCLUSIONS: Residual posterior SRF is more common in eyes with multiple breaks or in myopic eyes. Final BCVA is better in younger subjects and in eyes with shorter duration of RRD. Persistent SRF is a self-limited disorder with a mean resolution of 11.2 months with good visual prognosis improving from a mean baseline logMAR of 1.08 to 0.25 at one year.

Clinical characteristics of full thickness macular holes that closed without surgery.

PURPOSE: To ascertain the anatomic factors that help achieve non-surgical sealing in full thickness macular hole (FTMH). METHODS: Retrospective collaborative study of FTMH that closed without surgical intervention. RESULTS: A total of 78 patients (mean age 57.9 years) included 18 patients with blunt ocular trauma, 18 patients that received topical or intravitreal therapies and 42 patients with idiopathic FTMH. Mean±SD of the initial corrected visual acuity (VA) in logMAR improved from 0.65±0.54 to 0.34±0.45 (p<0.001) at a mean follow-up of 33.8±37.1 months. FTMH reopened in seven eyes (9.0%) after a mean of 8.6 months. Vitreomacular traction was noted in 12 eyes (15.8%), perifoveal posterior vitreous detachment in 42 (53.8%), foveal epiretinal membrane in 10 (12.8%), cystoid macular oedema (CME) in 49 (62.8%) and subretinal fluid (SRF) in 20 (25.6%). By multivariate analysis, initial VA correlated to the height (p<0.001) and narrowest diameter of the hole (p<0.001) while final VA correlated to the basal diameter (p<0.001). Time for closure of FTMH (median 2.8 months) correlated to the narrowest diameter (p<0.001) and the presence of SRF (p=0.001). Mean time for closure (in months) was 1.6 for eyes with trauma, 4.3 for eyes without trauma but with therapy for CME, 4.4 for eyes without trauma and without therapy in less than 200 µm in size and 24.7 for more than 200 µm. CONCLUSION: Our data suggest an observation period in new onset FTMH for non-surgical closure, in the setting of trauma, treatment of CME and size <200 µm.

Spectral transmittance of intraocular lenses under natural and artificial illumination: criteria analysis for choosing a suitable filter.

PURPOSE: To compare the spectral transmission of different intraocular lenses (IOLs) with either ultraviolet (UV) or blue-light filters, and to analyze the performance of these filters with artificial light sources as well as sunlight. DESIGN: Experimental study. METHODS: The spectral transmission curve of 10 IOLs was measured using a PerkinElmer Lambda 800 UV/VIS spectrometer (Waltham, MA). Different filtering simulations were performed using the D65 standard illuminant as daylight and standard incandescent lamp and fluorescent bulb illuminants. MAIN OUTCOMES MEASURES: Spectral transmittance of the IOLs. RESULTS: All the IOLs studied provide good UVC (200-280 nm) and UVB (280-315 nm) protection, except for one that presented an appreciable window at 270 nm. Nevertheless, both natural and artificial sources have practically no emission under 300 nm. In the UVA (315-380 nm) range the curves of the different IOLs manifested different degrees of absorption. CONCLUSIONS: Not all the UV filters incorporated in different IOLs protect equally. The filters that provide greater photoprotection against UV radiation, even blue light, are yellow and orange. Then, yellow and orange IOL filters may be best suited for cases requiring special retinal protection. The filters that favor better photoreception of visible light (380-780 nm) are those that transmit this radiation close to 100%. Artificial illumination practically does not emit in the UV range, but its levels of illumination are very low when compared with solar light. A possible balance between photoprotection and photoreception could be a sharp cutoff filter with the cutoff wavelength near 400 nm and a maximum transmittance around 100%.

Combined therapy: photodynamic therapy and bevacizumab to treat myopic neovascular membranes. One-year follow-up.

PURPOSE: The purpose of this study was to evaluate whether combined customized photodynamic therapy (PDT) and bevacizumab in myopic choroidal neovascularization can improve vision and whether it is possible to decrease the frequency and number of intravitreal antiangiogenic injections. METHODS: A prospective, consecutive, noncomparative, interventional case series of 36 patients with myopic choroidal neovascularization, treated with an initial dose of PDT and intravitreal bevacizumab 48 hours to 60 hours afterward. Retreatments were carried out as required with monthly bevacizumab and PDT every 3 months if there were relapses. Follow-up lasted 1 year in all cases. RESULTS: The mean best-corrected visual acuity increased from 44 letters before the initial treatment to 59.5 letters at the 12-month follow-up (P < 0.01). Compared with initial vision, 94.5% of the eyes had the same or better vision and 5.5% lost fewer than 6 lines of vision. The mean number of PDT treatments was 1.1 per patient, and the mean number of bevacizumab injections was 1.5 per patient. Only 1 initial treatment with PDT + bevacizumab was necessary in 28 cases (77.8%). CONCLUSION: Combined personalized PDT + bevacizumab therapy makes it possible to obtain visual results similar to those obtained in monotherapy studies but with fewer intravitreal injections. It appears to be an interesting option for this type of patient.

Lipid Peroxidation in Subretinal Fluid: Some Light on the Prognosis Factors.

The aim of this study was to identify a relation between the clinical characteristics and differences in lipid peroxidation in the subretinal fluid (SRF) of rhegmatogenous retinal detached patients by malondialdehyde (MDA) quantification. We collected 65 SRF samples from consecutive patients during scleral buckling surgery in rhegmatogenous retinal detachment (RRD) eyes. In addition to a complete ophthalmic evaluation, we studied the refractive status, evolution time, and the number of detached retinal quadrants to establish the extension of RRD. We studied the clinical aspects and oxidative stress and compared the characteristics among groups. We found that neither the evolution time of RRD nor the patients' age correlated with the MDA concentration in the SRF. The MDA and the protein content of the SRF increased in the patients with high myopia and with more extended RRD. Our results suggest that oxidative imbalance was important in more extended retinal detachment (RD) and in myopic eyes and should be taken into account in the managing of these cases.

High Myopia and the Complement System: Factor H in Myopic Maculopathy.

High myopia (HM) is both a medical problem and refractive error of the eye owing to excessive eyeball length, which progressively makes eye tissue atrophic, and is one of the main causes for diminishing visual acuity in developed countries. Despite its high prevalence and many genetic and proteomic studies, no molecular pattern exists that explain the degenerative process underlying HM, which predisposes patients to other diseases like glaucoma, cataracts, retinal detachment and chorioretinal atrophy that affect the macular area. To determine the relation between complement Factors H (CFH) and D (CFD) and the maculopathy of patients with degenerative myopia, we studied aqueous humor samples that were collected by aspiration from 122 patients during cataract surgery. Eyes were classified according to eyeball axial length as high myopia (axial length > 26 mm), low myopia (axial length 23.5-25.9 mm) and control (axial length ˂ 23.4 mm). The degree of maculopathy was classified according to fundus oculi findings following IMI's classification. Subfoveal choroid thickness was measured by optical coherence tomography. CFH and CFD measurements were taken by ELISA. CFH levels were significantly high in the high myopia group vs. the low myopia and control groups (p ˂ 0.05). Significantly high CFH values were found in those eyes with choroid atrophy and neovascularization (p ˂ 0.05). In parallel, the CFH concentration correlated inversely with choroid thickness (R = -0.624). CFD levels did not correlate with maculopathy. All the obtained data seem to suggest that CFH plays a key role in myopic pathology.

Validation of Automated Screening for Referable Diabetic Retinopathy With an Autonomous Diagnostic Artificial Intelligence System in a Spanish Population.

PURPOSE: The purpose of this study is to compare the diagnostic performance of an autonomous artificial intelligence (AI) system for the diagnosis of referable diabetic retinopathy (RDR) to manual grading by Spanish ophthalmologists. METHODS: Subjects with type 1 and 2 diabetes participated in a diabetic retinopathy (DR) screening program in 2011 to 2012 in Valencia (Spain), and two images per eye were collected according to their standard protocol. Mydriatic drops were used in all patients. Retinal images-one disc and one fovea centered-were obtained under the Medical Research Ethics Committee approval and de-identified. Exams were graded by the autonomous AI system (IDx-DR, Coralville, Iowa, United States), and manually by masked ophthalmologists using adjudication. The outputs of the AI system and manual adjudicated grading were compared using sensitivity and specificity for diagnosis of both RDR and vision-threatening diabetic retinopathy (VTDR). RESULTS: A total of 2680 subjects were included in the study. According to manual grading, prevalence of RDR was 111/2680 (4.14%) and of VTDR was 69/2680 (2.57%). Against manual grading, the AI system had a 100% (95% confidence interval [CI]: 97%-100%) sensitivity and 81.82% (95% CI: 80%-83%) specificity for RDR, and a 100% (95% CI: 95%-100%) sensitivity and 94.64% (95% CI: 94%-95%) specificity for VTDR. CONCLUSION: Compared to manual grading by ophthalmologists, the autonomous diagnostic AI system had high sensitivity (100%) and specificity (82%) for diagnosing RDR and macular edema in people with diabetes in a screening program. Because of its immediate, point of care diagnosis, autonomous diagnostic AI has the potential to increase the accessibility of RDR screening in primary care settings.

Use in clinical practice of an automated screening method of diabetic retinopathy that can be derived using a diagnostic artificial intelligence system. / Uso en la práctica clínica, de un método de cribado automatizado de retinopatía diabética derivable mediante un sistema de inteligencia artificial de diagnóstico.

BACKGROUND AND OBJECTIVE: To compare the diagnostic performance of an autonomous diagnostic artificial intelligence (AI) system for the diagnosis of derivable diabetic retinopathy (RDR) with manual classification. MATERIALS AND METHODS: Patients with type 1 and type 2 diabetes participated in a diabetic retinopathy (DR) screening program between 2011-2012. 2 images of each eye were collected. Unidentifiable retinal images were obtained, one centered on the disc and one on the fovea. The exams were classified with the autonomous AI system and manually by anonymous ophthalmologists. The results of the AI system and manual classification were compared in terms of sensitivity and specificity for the diagnosis of both (RDR) and diabetic retinopathy with decreased vision (VTDR). RESULTS: 10,257 retinal inages of 5,630 eyes of 2,680 subjects were included. According to the manual classification, the prevalence of RDR was 4.14% and that of VTDR 2.57%. The AI system recorded 100% (95% CI: 97-100%) sensitivity and 81.82% (95% CI: 80 -83%) specificity for RDR, and 100% (95% CI: 95-100%) of sensitivity and 94.64% (95% CI: 94-95%) of specificity for VTDR. CONCLUSIONS: Compared to the manual classification, the autonomous diagnostic AI system registered a high sensitivity (100%) and specificity (82%) in the diagnosis of RDR and macular edema in people with diabetes. Due to its immediate diagnosis, the autonomous diagnostic AI system can increase the accessibility of RDR screening in primary care settings.

IL-2 and IFN-gamma in the retina of diabetic rats.

BACKGROUND: The pathophysiology of the early events leading to diabetic retinopathy is not fully understood. It has been suggested that Inflammatory processes are involved in the development of the disease; however, the concentrations of tissue retinal inflammatory mediators and their possible alteration in diabetic retinopathy have not been described. The aim of this work was to study T-helper cell cytokine and chemokine profiles, and tyrosine nitration in retinal tissue of diabetic rats. METHODS: Cytokines (interleukin IL-1a, IL-1b, IL-2, IL-4, IL-6, IL-10, TNFa, GM-CSF, IFN-g), chemokines (MIP-1a, MIP-2, MIP-3a, MCP-1, GRO/KC, RANTES, Fractalkine), and tyrosine nitration were measured in retinal homogenate obtained from Long-Evans rats after 5 months of experimental diabetes. RESULTS: The T-helper type 1 cytokines IL-2 and INF-gamma, in addition to NO production (measured as nitrotyrosine), were found to be significantly elevated in diabetic rat retina homogenates. None of the other cytokines and chemokines studied were affected by the diabetic condition. CONCLUSIONS: Immunoregulatory cytokines belonging to the Th-1 group (IL-2 and IFN-gamma) were increased in the retina of experimental diabetic rats. Moreover, the nitrotyrosine formation (as an expression of increased NO production) was significantly elevated in the diabetic retina, supporting the concept of an inflammatory element in the development of diabetic retinopathy.

Combined ranibizumab and photodynamic therapy to treat exudative age-related macular degeneration: an option for improving treatment efficiency.

PURPOSE: The purposes of this study were to determine whether the association of photodynamic therapy (PDT) and intravitreal ranibizumab could improve vision in a group of patients with choroidal neovascularization secondary to age-related macular degeneration and whether it could reduce the number and frequency of intravitreal injections, thus minimizing adverse effects. METHODS: A nonrandomized, prospective, interventional study was conducted of a case series of 53 patients with sub- and juxtafoveal choroidal neovascularization secondary to age-related macular degeneration treated with a single initial dose of PDT and intravitreal ranibizumab. Retreatments were performed as required with monthly ranibizumab and PDT every 3 months if there were relapses. The retreatment criteria were based on visual acuity, optical coherence tomography, and fluorescein angiography. Follow-up lasted 12 months in all cases. RESULTS: The mean initial visual acuity was 40.6 letters versus 47.8 letters at the end of follow-up with a gain of 7.2 letters (P < 0.001). Moreover, 78.8% maintained or improved their initial vision, and 92.3% avoided moderate vision loss (>15 letters). A total of 65 PDT treatments (mean, 1.22 per patient) was performed and 126 doses of ranibizumab were injected (mean, 2.37 per patient). Only a single initial dose (PDT + ranibizumab) was required in 21 cases (39.6%). The central retinal thickness and choroidal neovascularization size decreased to 118 microm and 0.26 disk areas, respectively, from baseline to 12 months. CONCLUSION: Combined customized PDT + ranibizumab treatment can achieve visual results similar to those obtained with intravitreal monotherapy with the advantage of fewer intravitreous injections and reduced potential for adverse effects.