Long-term full-field and multifocal electroretinographic changes after treatment with ranibizumab in patients with diabetic macular edema.

PURPOSE: To investigate changes in macular and panretinal neuroretinal functions by electroretinographic examinations in eyes with diabetic macular edema (DME) treated with intravitreal ranibizumab. MATERIAL AND METHODS: Sixty-four patients with DME were included in this prospective study. Patients were treated with ranibizumab injection according to the PRN regimen for over 12 months. Before treatment, all patients underwent fundus fluorescein angiography, optical coherence tomography (OCT), best-corrected visual acuity (BCVA) assessment, full-field (ff-ERG), and multifocal electroretinography (mf-ERG). In monthly visits, BCVA and OCT were performed. Besides, mf-ERG recordings were obtained at months 3, 6, 9, and 12, and ff-ERG was performed at month 12. RESULTS: Fifty-eight patients completed the study. The mean age was 61.1 ± 8.5 (39-80) years. The mean number of injections was 6.19 ± 1.9. The decimal BCVA improved from 0.30 to 0.45 during the 12-month follow-up (p < 0.05). Macular thickness decreased from 413.5 µm to 329.5 µm (p < 0.05). The mf-ERG recordings in the central macular region showed improvements N1 and P1 amplitudes at months 9 and 12. There was a positive correlation between the baseline central (p < 001; r: - 0.378 and p < 0.05; r:-0.335, respectively), the second ring (p < 0.05; r: - 0.260 and p < 0.05; r: - 0.270, respectively) P1- and N1-wave amplitudes, and the BCVA at month 12. Full-field ERG recordings showed that peripheral neuroretinal responses were maintained or improved at month 12. Statistically significant improvements in BCVA and macular thickness were observed at all follow-up visits. CONCLUSION: Multifocal electroretinographic recording started to improve 6 months after the beginning of intravitreal ranibizumab treatment in eyes with DME. This improvement was significant at months 9 and 12. A significant improvement in ff-ERG was observed at month 12.

Comparison of Long-Term Automated Retinal Layer Segmentation Analysis of the Macula between Silicone Oil and Gas Tamponade after Vitrectomy for Rhegmatogenous Retinal Detachment.

PURPOSE: To identify long-term changes in individual retinal layer thickness using automated retinal layer segmentation analysis on high-resolution spectral-domain optical coherence tomography (SD-OCT) scans of eyes with macula-off rhegmatogenous retinal detachment (RRD) treated with vitreoretinal surgery (VRS) and gas or silicone oil tamponade and having single-operation success. METHODS: A total of 58 patients operated on by VRS for RRD and followed up for 12 months were imaged by SD-OCT. The patients with retinal diseases such as an epiretinal membrane or cystic macular edema in the operated and fellow eyes were excluded. The thicknesses of the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), photoreceptor layer, and retinal pigment epithelium were compared to those of the fellow eyes after the 12-month follow-up. Thickness changes in individual layers were quantitatively analyzed in the operated and fellow eyes and correlated with the type of tamponade used in the surgery. RESULTS: Spectralis OCT automated segmentation software was used for the retinal layer analysis. There were 22 females and 36 males. Their mean age was 60.7 ± 11.2 years. The mean central macular thickness was 214.3 ± 29.5 µm in the operated and 229.7 ± 21.7 µm in the fellow eyes (p = 0.008). There was a statistically significant difference between the operated and the healthy fellow eyes in the following layers: the RNFL (p = 0.017), GCL (p = 0.02), INL (p = 0.005), and ONL (p = 0.008) in the central foveal area; the RNFL (p < 0.001), INL (p = 0.017), and ONL (p = 0.022) in the perifoveal ring; and the RNFL (p < 0.001), IPL (p = 0.042), INL (p = 0.001), and OPL (p = 0.001) in the peripheral ring. The logMAR best corrected visual acuities were 2.51 ± 0.68 and 2.69 ± 0.62 at baseline and 0.60 ± 0.38 and 0.50 ± 0.38 at month 12 in the silicone oil tamponade (n = 28) and the gas tamponade (n = 30) group (p = 0.52 and p = 0.21, respectively). The foveal GCL, OPL, and ONL and the perifoveal GCL and IPL were statistically significantly thinner in the silicone oil tamponade group (p = 0.01, p = 0.046, p = 0.024, p = 0.006, and p = 0.011, respectively). CONCLUSIONS: Significant changes were observed in the retinal layers after VRS for RRD. Individual retinal layers seem to be affected 1 year after VRS for RRD. The type of tamponade can influence the thickness of the retinal layers. The thickness of the retinal layers was significantly preserved in eyes treated with gas tamponade when compared to those treated with silicone oil tamponade in the long term. Further studies are needed to validate our results.

Comparison of navigated laser and conventional single-spot laser system for induced pain during panretinal photocoagulation.

To compare the panretinal photocoagulation (PRP)-induced pain response between novel navigated laser (Navilas) and conventional single-spot laser. The eyes were randomly assigned to Navilas or conventional laser. Contralateral eyes underwent PRP with the other system with 30 min resting interval. Pulse duration was 100 ms in conventional laser and 30 ms or 100 ms in Navilas and power setting was enough to create gray-white light burn on both devices. Pain response was evaluated by verbal scale (VS) (0-4) and visual analog scale (VAS) (0-10) after each PRP application. The mean age of 70 patients (140 eyes) was 62.52 ± 9.49 years. Mean power and spot numbers for Navilas and conventional laser were 291.9 ± 85.3 mW vs 368.4 ± 72.0 mW, and 375.4 ± 108.4 vs 374.2 ± 105.0 (p < 0.001 and p = 0.53, respectively). Pain scores for Navilas and conventional laser were 1.19 ± 0.73 and 1.99 ± 0.84 for VS and 2.41 ± 1.65 and 4.74 ± 2.17 for VAS (p < 0.001 and p < 0.001). More comfortable PRP is achieved with Navilas system in comparison with conventional single-spot laser system. However, small number of patients treated with same pulse duration and different contact lenses used for two systems should be taken into consideration. Besides, we did not report comparative clinical efficiency of either laser system.

The association of exudation pattern with anatomical and functional outcomes in patients with Neovascular Age-Related Macular Degeneration.

Objective. To evaluate the correlation between visual outcomes and fluid configuration observed on spectral-domain optical coherence tomography (SD-OCT) in patients with wet age-related macular degeneration (AMD). Methods. Sixty-five eyes of 53 patients with AMD who were administered intravitreal ranibizumab treatment with 12 months of follow-up were included in this retrospective study. Presence of intraretinal cystoid fluid (IRC) and pigment epithelial detachment (PED), thickness of subretinal fluid (SRF), central macular thickness (CMT), and central macular volume (CMV) were assessed. Results. Subretinal fluid was observed in 29 eyes (45%), IRC in 36 eyes (55%), and PED in 39 eyes (60%). Baseline and final best-corrected visual acuity (BCVA) were 0.69±0.4 and 0.60±0.4 logMAR in the IRC negative group and 1.17±0.5 and 0.97±0.5 logMAR in the IRC positive group. BCVA was lower in IRC positive group (baseline p=0.001 and final=0.003); however, marked improvement was detected in both groups. Anatomic improvement and increased visual acuity were observed in groups with and without PED, IRC, and SRF. An inverse correlation was detected between pre-treatment CMT, IRC and post-treatment IRC, and final BCVA. Conclusion. Significant visual and anatomic improvement was observed after one-year of ranibizumab treatment regardless of fluid configuration. However, the presence of IRC was observed to be associated with worse visual acuity. Baseline retinal fluid configuration may have prognostic effects on functional success in patients treated with ranibizumab for wet AMD. Abbreviations. AMD = Age-related macular degeneration, VEGF = Vascular endothelial growth factor, IRC = intraretinal cystoid fluid, PED = pigment epithelial detachment, SRF = subretinal fluid, SD-OCT = spectral-domain ocular coherence tomography, IVR = intravitreal ranibizumab, BCVA = best-corrected visual acuity, FFA = fundus fluorescein angiography, CMT = central macular thickness, CMV = central macular volume.

Long-term changes in retinal layers in patients undergoing intravitreal ranibizumab for neovascular age-related macular degeneration : Retinal layers after anti-VEGF therapy.

PURPOSE: To analyze long-term changes in individual retinal layers (RLs) after intravitreal injections of ranibizumab (IVRs) in patients with neovascular age-related macular degeneration (n-AMD). METHODS: The patients were treated with 0.5-mg IVRs based on an as-needed protocol after the first three monthly doses over a 12-month follow-up period. Patients underwent optical coherence tomography and best-corrected visual acuity (BCVA) evaluation at each visit. The ETDRS grid with central subfield (R1) (r 0.5 mm) and the inner ring (R2) (r 0.5-1.5 mm) was used for calculation of the mean thickness of each RL. Changes in the thickness of segmented RLs within the R1 and R2 of ETDRS circles at months-3, -6, and -12 were compared to baseline. RESULTS: The mean age was 72 ± 7.4 years. The mean number of injections was 9.08 (range 6-11). Mean BCVA improved from 49.7 ± 22.1 to 60.1 ± 19.8 letters. Central macular thickness decreased from 390.25 ± 149.6 to 312.74 ± 118.4 µm. Thicknesses of GCL (from 23.93 ± 13.73 to 19.50 ± 9.50 µm in R1; p 0.001, and from 44.5 ± 12.6 to 39.6 ± 10.6 µm in R2; p 0.005), IPL (from 28.90 ± 14.36 to 22.35 ± 6.23 µm in R1; p 0.001, and from 39.34 ± 8.53 to 35.58 ± 7.93 µm in R2; p 0.004), and total inner RL (ILM to ELM) (from 222.93 ± 93.09 to 180 ± 53 µm in R1; p 0.001, and from 255.06 ± 42.74 to 240.25 ± 40.37 µm in R2; p 0.003) in the central and parafoveal rings decreased statistically at month-12. Decrease in INL was limited to month-6 (from 34.80 ± 15.33 to 27.60 ± 12.59 µm in R1; p 0.001), while decreases in total outer RLs (ELM to RPE) (from 128.32 ± 26.92 to 115.54 ± 43.98 µm in R1; p 0.001, and 103.81 ± 16.73 to 96.38 ± 16.22 µm in R2; p 0.014) and RPE (from 39.12 ± 22.33 to 29.70 ± 22.05 µm in R1; p 0.001, and from 31.27 ± 13.11 to 24.40 ± 9.99 µm in R2; p 0.001) were limited to month-3. CONCLUSIONS: Significant changes were observed in the thickness of the inner RLs after 1-year treatment with IVRs for n-AMD. A significant decrease in RPE thickness confined to the first months disappeared at month-12.

Long-Term Changes in Submacular Choroidal Thickness after Intravitreal Ranibizumab Therapy for Neovascular Age-Related Macular Degeneration: 14-Mo Follow-Up.

Purpose: To study (i) the long-term effects of intravitreal ranibizumab treatment on changes in submacular choroidal thickness and (ii) the relationship between any resulting changes in choroidal thickness and visual outcomes following such treatment in patients with neovascular age-related macular degeneration (n-AMD). Methods: Reviewed were medical records of 30 consecutive, treatment-naïve, patients with unilateral n-AMD (n = 30 eyes) and unaffected fellow eyes (n = 26 eyes) (controls). Monthly injections of 0.5 mg ranibizumab were administered until stabilization of n-AMD, with additional injections as needed over the following 14-mo. Choroidal thickness was determined using enhanced-depth imaging-optical coherence tomography (EDI-OCT) before and after initiation of ranibizumab therapy. Choroidal thickness measurements were generated via manual segmentation. Results: The mean age of patients was 71.9 ± 7.4 (56-83) years; the mean best-corrected visual acuity (BCVA) of affected eyes improved from 51.1 to 59.4 letters (p < 0.001); and the mean number of injections was 9.16 ± 1.75. Subfoveal choroidal thickness decreased from 208.3 ± 73.7 µm at baseline to 185.3 ± 70.1 µm at mo-14 (p < 0.001), with significant (p < 0.001) decreases at all measured time points. Choroidal thickness also tended to decline in fellow eyes but was only statistically significant nasally 1,000 µm (p =0.04). Mean changes in choroidal thickness did not correlate with BCVA at mo-14 (p = 0.76). Disciform scars and geographic atrophy (p = 0.017), and BCVA (p < 001) at baseline were predictive of visual outcome. Age (p = 0.001), reticular drusen (p = 0.004), and size of choroidal neovascularized area (p = 0.042) were predictive of decreases in choroidal thickness. Conclusions: Submacular choroidal thickness appeared to decrease significantly in eyes with n-AMD over a 14-mo period of ranibizumab treatment. No corresponding decrease in choroidal thickness occurred in fellow eyes.

Quality of life among patients with age-related severe macular degeneration assessed using the NEI-VFQ, HADS-A, HADS-D and SF-36 tests. A cross-sectional study

ABSTRACT BACKGROUND: Exudative age-related macular degeneration (e-AMD) may cause severe central vision loss. Patients with e-AMD can experience difficulties in daily basic activities and suffer from psychological problems. Our aim was to assess quality of life (QoL) and anxiety and depression status among patients with e-AMD. DESIGN AND SETTING: Cross-sectional study in a state university. METHODS: We included 200 e-AMD patients and 120 age and gender-matched controls. We assessed QoL using the National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) and the Short Form (SF)-36 test; and anxiety and depression status using the Hospital Anxiety Depression Scales A and D (HADS-A and HADS-D). RESULTS: The mean ages in the e-AMD and control groups were 68.40 ± 9.8 and 66.31 ± 8.98, respectively. Visual acuity among e-AMD patients was 0.37 ± 0.31 and 0.39 ± 0.32 in the right and left eyes, respectively. The e-AMD patients performed significantly worse than the controls in NEI-VFQ-25 (P < 0.05 for all items). The proportions of e-AMD patients scoring higher than the cutoffs in HADS-A and HADS-D were significantly higher than among the controls (41.5% versus 12.5% and 63.5% versus 27.5%; P < 0.001). The e-AMD patients had significantly lower mean scores than the controls for each of the SF-36 QoL items (P < 0.001). The NEI-VFQ-25 scores were significantly lower among patients with bilateral e-AMD than among those with unilateral disease (P < 0.05 for all). The HADS scores were positively correlated with duration of e-AMD and patient age, but negatively with vision levels (P < 0.05 for all items). CONCLUSION: The e-AMD patients had higher depression and anxiety scores and lower QoL scores.

VITREORETINAL SURGERY FOR PATIENTS WITH SEVERE EXUDATIVE AND PROLIFERATIVE MANIFESTATIONS OF RETINAL CAPILLARY HEMANGIOBLASTOMA BECAUSE OF VON HIPPEL-LINDAU DISEASE.

PURPOSE: The evaluation of long-term results of vitreoretinal surgery and retinal capillary hemangioblastoma (RCH) resection in patients with complicated retinal detachment (RD) secondary to RCHs. METHODS: Twelve eyes of 12 patients were operated on with vitreoretinal surgery, including occlusion of afferent and efferent feeder vessels with endodiathermy and endolaser photocoagulation, and subsequent resection of RCHs. The long-term anatomical and visual outcomes were retrospectively evaluated. RESULTS: Total exudative RD was detected in six eyes and subtotal exudative RD was found in the remaining six eyes. A tractional component was present in eight eyes, and four eyes had pure exudative RD. Laser treatment had been previously applied to four eyes but vitreoretinal surgery was the primary treatment in eight eyes. A total of 19 RCHs were resected. The quadrant location of RCHs was superior temporal in six, superior nasal in five, inferior nasal in five, and inferior temporal in three. The dimensions of the RCHs ranged between 1 and 4 disk diameters (DD) (1-DD in 1 eye, 1.5-DD in 3, 2-DD in 10, 2.5-DD in 3, 3-DD in 1, and 4-DD in 1). Preoperative mean logarithm of the minimum angle of resolution visual acuity was 1.9 ± 1.0 (3.0-0.7) (20/1,588 ± 20/200 [20/20,000-20/100]). Silicone oil and C3F8 was applied to four and eight eyes, respectively. The median postoperative follow-up was 30.5 (18-48) months. Single operation and final anatomical success was obtained in 9 and 11 eyes, respectively. Mean logarithm of the minimum angle of resolution visual acuity in the postoperative 18th month and at the final visit were 1.05 ± 0.8 (3.0-0.2) (20/224 ± 20/125 [20/20,000-20/32]) and 0.96 ± 0.8 (3.0-0.2) (20/182 ± 20/125 [20/20,000-20/32]), respectively. New RCHs occurred in eight eyes. Rubeosis iridis was not present in any of the eyes. CONCLUSION: Promising anatomical and visual outcomes were obtained after vitreoretinal surgery and resection of RCHs in eyes with complicated RD secondary to RCH. However, life-long follow-up is needed to recognize recurrent RD seen even in the early period or recurrences of RCHs seen in the long-term period.

Comparison of pain scores between patients undergoing panretinal photocoagulation using navigated or pattern scan laser systems / Comparação de graduação de dor entre os pacientes submetidos à panfotocoagulação usando sistemas de laser navegado ou de padrão de varredura

ABSTRACT Purpose: To compare the pain responses of patients with proliferative diabetic retinopathy (PDR) undergoing panretinal photocoagulation (PRP) using either pattern scan laser (PASCAL) or navigated laser photocoagulation (NAVILAS). Methods: Patients diagnosed with PDR were randomly assigned to undergo either PASCAL or NAVILAS photocoagulation treatment. PRP was performed using the multi-shot mode with a spot size of 200-400 µm and a pulse duration of 30 ms to obtain a white-grayish spot on the retina. Parameters were identical in both procedures. After 30 min of PRP application, patients were asked to verbally describe their pain perception as either "none," "mild," "moderate," "severe," or "very severe" using a verbal rating scale (VRS) and visual analog scale (VAS) by indicating a score from "0" to "10," representing the severity of pain from "no pain" to "severe pain." Results: A total of 60 eyes of 60 patients (20 females and 40 males) diagnosed with PDR were treated. The mean age of patients was 62.22 ± 9.19 years, and the mean diabetes duration was 195.47 ± 94.54 months. The mean number of laser spots delivered during PRP was 389.47 ± 71.52 in the NAVILAS group and 392.70 ± 54.33 in the PASCAL group (p=0.57). The difference in pain responses between patients in the NAVILAS and PASCAL groups was significant with regard to the mean VRS (1.10 ± 0.67 and 1.47 ± 0.69, respectively; p=0.042) and mean VAS (2.13 ± 1.17 and 2.97 ± 1.35, respectively; p=0.034) scores. Conclusions: Pain responses in patients undergoing PRP with a 30-ms pulse duration were significantly milder in the NAVILAS group than in the PASCAL group.

RESUMO Objetivo: Comparar as respostas de dor de pacientes com retinopatia diabética proliferativa (PDR) submetidos à panfotocoagulação retiniana (PRP) usando laser de padrão de varredura (PASCAL) ou fotocoagulação navegada a laser (NAVILAS). Métodos: Pacientes com diagnóstico de PDR foram aleatoriamente designados para submeter-se ao tratamento de fotocoagulação com PASCAL ou NAVILAS. A PRP foi realizada no modo "multi-shot" com diâmetro do laser de 200-400 µm e duração do pulso de 30 ms, utilizados para se obter uma mancha branca-acinzentada na retina. Os parâmetros foram idênticos em ambos os procedimentos. Após 30 minutos da PRP, os pacientes foram solicitados a descrever verbalmente a sua percepção da dor como quer "nenhuma," "leve," "moderada," "intensa" ou "dor muito intensa" por meio de uma escala de avaliação verbal (VRS) e também por meio de uma escala visual analógica (VAS), indicando uma pontuação de "0" a "10" representando a intensidade da dor de "nenhuma dor" a "dor intensa." Resultados: Um total de 60 olhos de 60 pacientes (20 mulheres e 40 homens) com diagnóstico de PDR foram tratados. A média de idade dos pacientes foi de 62,22 ± 9,19 anos e a média de duração da diabete foi 195.47 ± 94,54 meses. O número médio de pulsos de laser emitidos durante a PRP foi 389,47 ± 71,52 no grupo NAVILAS e 392,70 ± 54,33 no grupo PASCAL (p=0,57). A diferença nas respostas de dor entre os pacientes nos grupos NAVILAS e PASCAL foi significativa em relação às médias de VRS (1,10 ± 0,67 e 1,47 ± 0,69; p=0,042) e VAS (2,13 ± 1,17 e 2,97 ± 1,35; p=0,034). Conclusões: As respostas de dor em pacientes submetidos à PRP com pulsos de 30 ms de duração foram significativamente menores nos pacientes do grupo NAVILAS em relação ao grupo PASCAL.

Bilateral isolated lens coloboma associated with bicuspid aortic valve / Coloboma de cristalino bilateral isolado associado à valva aórtica bicúspide

ABSTRACT A 27-year-old woman presented with a history of long-standing poor vision in both eyes. Ophthalmologic examination after pupillary dilatation revealed bilateral lens coloboma situated in the inferotemporal quadrant. No associated ocular abnormalities were seen, except amblyopia. A bicuspid aortic valve was observed during echocardiography during systemic evaluation. Lens coloboma usually occurs unilaterally; however, bilateral lens coloboma which is isolated or associated with other ocular malformations is also encountered. This is the first description of bilateral isolated lenticular coloboma associated with bicuspid aortic valve. Although the association between bicuspid aortic valve and lens coloboma may be an incidental finding, they may be components of an unknown syndrome.

RESUMO Uma mulher de 27 anos apresentou-se com uma história de longa data de deficiência visual em ambos os olhos. O exame oftalmológico após dilatação pupilar revelou coloboma de cristalino bilateral localizado no quadrante temporal inferior. Nenhuma outra alteração ocular associadas foi observada, exceto ambliopia. A valva aórtica bicúspide foi diagnosticada no exame de ecocardiograma durante a avaliação sistêmica. Coloboma cristaliniano ocorre geralmente de forma unilateral, no entanto já foi descrito bilateralmente, associado a outras malformações oculares ou isolado. Esta é a primeira descrição de coloboma cristaliniano isolado bilateral associado à valva aórtica bicúspide. Embora a associação de valva aórtica bicúspide e coloboma cristaliniano no nosso caso pode ter sido um achado incidental, eles podem ser componentes de uma síndrome desconhecida.

Evaluation of cystoid macular edema using optical coherence tomography and fundus fluorescein angiography after uncomplicated phacoemulsification surgery.

PURPOSE: To evaluate the central macular thickness (CMT) and the cystoid macular edema (CME) after uncomplicated phacoemulsification surgery. MATERIAL AND METHODS: Ninety-one eyes of 88 patients who underwent uncomplicated phacoemulsification surgery between December 2008 and May 2009 were included in the study. Detailed ophthalmologic examinations and spectral domain optical coherence tomography (OCT) measurements were done preoperatively and at postoperative 1st, 4th, 12th, and 24th weeks. Best corrected visual acuity (BCVA) was measured as logMAR units at preoperative and all postoperative visits. Mean CMT, and perifoveal macular thickness in superior, inferior, nasal and temporal quadrants were recorded. CME was defined as three standard deviations (SD) above the preoperative mean CMT in OCT measurements. Fundus fluorescein angiography (FFA) was performed at postoperative 12th weeks. Data was analyzed statistically by using ANOVA test, and paired samples t test with Bonferroni correction. RESULTS: The mean preoperative CMT was 255.68 ± 23.04 µm. The increase in CMT was statistically significant at postoperative 1st, 4th, 12th, and 24th weeks (p = 0.043). The most significant increase in CMT was seen at 12th weeks (p = 0.028). The change in perifoveal macular thickness measurements in the temporal, nasal, superior and inferior quadrant was statistically significant at postoperative 12th weeks (p < 0.001, for all measurements). The increase in macular thickness did not correlate with BCVA at postoperative 1st and 4th weeks but there was a significant correlation at postoperative 12th and 24th weeks. The incidence of angiographic CME at postoperative 12th weeks was 3.2%. The appearance of CME in OCT was observed in 5.5% of eyes at postoperative 12th weeks. CONCLUSION: Macular thickness changes after uncomplicated phacoemulsification surgery and Spectral domain OCT is helpful in detecting cystoid abnormalities and any increase in macular thickness at postoperative early periods. Changes seen on OCT do not completely correlate with FFA findings.

Comparative evaluation of apoptotic activity in photoreceptor cells after intravitreal injection of bevacizumab and pegaptanib sodium in rabbits.

PURPOSE: To evaluate quantitatively the apoptotic activity after intravitreal injections of pegaptanib sodium and bevacizumab in the rabbit retina. METHODS: Different doses of bevacizumab (0.25, 0.625, 1.25, and 2.5 mg) and pegaptanib sodium (0.15, 0.3, and 0.6 mg) were injected intravitreally in 48 rabbits. The eyes were enucleated at different times for early studies at day 14 and for late studies at 3 months after a single injection or at 3 months, with 1 injection in each of the 3 months (day 90). The time course and dose-response of photoreceptor cells in the rabbit retina after intravitreal injection of bevacizumab or pegaptanib sodium were examined by histologic analysis with hematoxylin and eosin (H&E) staining, caspase-3 and -9 immunostaining, and in situ terminal-deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling (TUNEL) of DNA fragments of paraffin-embedded sections. RESULTS: No sign of retinal toxicity was seen in H&E stained histologic sections of eyes that had received bevacizumab or pegaptanib sodium. Nuclear DNA fragmentation in the outer retinal layers shown by the TUNEL method was evident in the high-dose groups (55.3% with 1.25 mg and 64.5% with 2.5 mg bevacizumab, and 48.5% with 0.6 mg pegaptanib sodium) at 14 days and also in the clinical dose groups (49.8% with three injections [1 each month] of 0.625 mg bevacizumab and 44.3% with 0.15 mg pegaptanib sodium) at 90 days. The ratios of TUNEL-positive cells in physiologic saline and the sham-control groups were 32.3% and 21%, respectively. CONCLUSIONS: Intravitreal injection of bevacizumab and pegaptanib sodium caused a significant increase in apoptotic activity in rabbit photoreceptor cells. However, although bevacizumab caused increasing apoptotic activity at higher doses, similar dose-dependent adverse effects were not evident for pegaptanib sodium.

Preclinical safety evaluation of intravitreal injection of full-length humanized vascular endothelial growth factor antibody in rabbit eyes.

PURPOSE: To evaluate the preclinical safety of intravitreal bevacizumab, which is a full-length humanized monoclonal antibody against the vascular endothelial growth factor (VEGF), in rabbit eyes over a short-term period. METHODS: Twenty-four rabbits were divided into two groups, each with two subgroups. The first group (groups 1 and 2) received 1.25 mg (0.05 mL) intravitreal bevacizumab, and the second group (groups 3 and 4) received 3.00 mg (0.12 mL) intravitreal bevacizumab. The right eyes were designated as the study eyes, and the left eyes served as a control and received the same volume of saline intravitreally. Groups 1 and 3 were labeled as early groups and scheduled to be terminated at 14 days. Groups 2 and 4, labeled as late groups, were scheduled to be terminated at 28 days. Besides electroretinography (ERG) and visually evoked potentials (VEP), central corneal thickness, intraocular pressure, fundus photography, and anterior segment imaging were performed at baseline and scheduled time points. Enucleated eyes were preserved for light and electron microscopic investigation. RESULTS: No anterior segment inflammation was observed, except in one eye in group 1 which showed a uveitic reaction. No evidence of retinal toxicity was seen with intravitreal bevacizumab at doses of 1.25 and 3.00 mg, by either ERG or light microscopy. Electron microscopic assessment revealed mitochondrial damage in the inner segments of photoreceptors. Immunohistochemical staining with bax and caspase-3 and -9 showed intensive apoptotic protein expression in all study sections and minimal expression in the control eyes. CONCLUSIONS: Although electrophysiologic investigation and light microscopy showed normal retinal function and structure, mitochondrial disruption in the inner segments of photoreceptors was detected by electron microscopy, and apoptotic expression was detected after the injection of intravitreal bevacizumab.

Effect of diclofenac on prevention of posterior capsule opacification in human eyes.

BACKGROUND: Diclofenac sodium has been demonstrated to be effective in preventing proliferation of lens epithelial cells both in vitro and in animal studies. The effects of diclofenac sodium given during the hydrodissection stage of phacoemulsification surgery on posterior capsule opacification (PCO) were investigated. METHODS: Eleven patients undergoing phacoemulsification in both eyes were included. Patients with pseudoexfoliation, uveitis, and diabetes were excluded. Hydrodissection was done with only balanced salt solution in the first eyes. In the fellow eyes, 0.25 mg/mL diclofenac was given with hydrodissection. The same type of intraocular lens was implanted in both eyes of each patient. Follow-up was 21.8 (SD 3.5) months in the diclofenac group and 22.9 (3.7) months in the control group. PCO was evaluated clinically by dividing the posterior capsule into 24 zones. Mann-Whitney U test was used for statistical analysis. RESULTS: There were no statistically significant differences of age, diameter of capsulorhexis, pupillary width, visual acuity, intraocular pressure, or length of follow-up between groups. PCO score was 0.49 (SD 0.21) in eyes receiving diclofenac and 0.73 (0.23) in the contralateral fellow eyes. The difference was not statistically significant (p=0.053). INTERPRETATION: Diclofenac sodium given by hydrodissection in phacoemulsification decreased, but did not significantly prevent, the development of PCO.

Characteristics of lacrimo-auriculo-dento-digital (LADD) syndrome: case report of a family and literature review.

We describe a family with lacrimo-auriculo-dento-digital syndrome (LADD). A 13-year-old boy had cup-shaped ears, deafness, unilateral choanal atresia, bilateral nasolacrimal duct obstruction, xerostomia, alacrima due to congenital absence of lacrimal glands, agenesis of salivary glands, chronic dacryocystitis, keratoconjunctivitis sicca, ptosis, nail dysplasia of the thumb, shortness of fifth toe, temporal bone abnormality and epilepsy. His younger sister had shortened middle phalanx of fifth digits. His middle sister had hypodontia, shortened distal phalanx of fifth digit, agenesis of salivary glands, mild hearing loss and exotropia. His older sister had left nasolacrimal duct obstruction and aplasia of both parotid glands. The oldest sister had hypodontia and divergent excess exotropia. His mother had hypodontia. These findings are consistent with LADD syndrome. An autosomal dominant pattern of inheritance with variable expressivity has been demonstrated. Renal and uro-genital anomalies have been noted variably.

Surgically induced astigmatism after superotemporal and superonasal clear corneal incisions in phacoemulsification.

PURPOSE: To evaluate surgically induced corneal astigmatism after small superotemporal and superonasal clear corneal incision cataract surgery. SETTING: Department of Ophthalmology, School of Medicine, University of Afyon Kocatepe, Afyon, Turkey. METHODS: This prospective study comprised 56 eyes of 28 patients who had bilateral phacoemulsification and implantation of a foldable intraocular lens (IOL) through a corneal tunnel incision. A superotemporal incision was used in all right eyes, and a superonasal incision was used in all left eyes. Topography was performed preoperatively and at 1 week, 1, 3, and 6 months, and 1 year. Surgically induced astigmatism (SIA) was calculated by vector analyses using the Holladay-Cravy-Koch method. The incision length was measured and was between 3.30 mm and 3.50 mm in all eyes. RESULTS: Although SIA did not differ significantly between the 2 incision groups (P>.05), decomposition of vectors showed that the horizontal component of SIA after superonasal incision was statistically significantly higher than superotemporal incision throughout the study (P<.05). Vertical components of SIA and the incision size after IOL implantation with the syringe/cartridge system between the 2 incision groups were not significantly different (P>.05). CONCLUSION: There was no statistically significant difference in SIA between superotemporal incisions in the right eyes and superonasal incisions in the left eyes 1 year after surgery for a surgeon who sits at the 12 o'clock. Superonasal clear corneal incisions can be used in left eyes and superotemporal clear corneal incisions in right eyes.

Effects of fentanyl on pain and hemodynamic response after retrobulbar block in patients having phacoemulsification.

PURPOSE: To determine the effects of systemic fentanyl analgesia in preventing the pain related to the administration of retrobulbar anesthesia and cataract surgery. SETTING: Departments of Ophthalmology and Anesthesiology, School of Medicine, Kocatepe University, Afyon, Turkey. METHODS: One hundred twenty patients with American Society of Anesthesiologists physical status I to III scheduled for cataract surgery were evaluated in a single-blind randomized study. Patients with a history of hypertension, hyperthyroidism, or neurologic or psychiatric disorders were excluded. In the study (fentanyl) group, an intravenous bolus of fentanyl 2 microg/kg was slowly given 5 minutes before retrobulbar anesthesia was administered. In the control group, fentanyl was not given. There were 60 patients in each group. Demographic data were not statistically different between the 2 groups. The intensity of pain during injection and intraoperatively was measured by verbal pain scores. Hemodynamic stability was assessed by the heart rate (HR) and mean arterial pressure (MAP). End-tidal carbon dioxide concentrations and oxygen saturations were also recorded. RESULTS: The changes in HR and MAP at 0, 10, 20, and 30 minutes were statistically significant between the fentanyl and control groups (P<.05). Fentanyl reduced pain scores significantly at all evaluations (P<.05). CONCLUSION: The results suggest that fentanyl preemptively decreases injection and intraoperative hyperalgesia and provides hemodynamic stability without affecting patient cooperation, resulting in cataract surgery with retrobulbar anesthesia that is comfortable for both surgeon and patient.