Effects of Topical or Intravitreal Application of Anti-Vascular Endothelial Growth Factor on Density of Intestinal Blood Vessels of Mice.

Background and Objectives: Anti-vascular endothelial growth factor (anti-VEGF) therapy has become the first-line treatment for diabetic macular edema. However, it is still not clear whether anti-VEGF agents act on systemic blood vessels. The aim of this study is to determine whether a direct topical application or intravitreal injection of anti-VEGF will change the intestinal blood vessels of mice. Materials and Methods: C57BL/6 mice were laparotomied under deep anesthesia, and the blood vessels on the surface of the intestines were exposed, examined, and photographed through a dissecting microscope. Vascular changes were evaluated before and at 1, 5, and 15 min after the topical application of 50 µL of the different anti-VEGF agents onto the surface of the intestine (group S) or after the intravitreal injection (group V). The vascular density (VD) was determined for five mice in each group before and after 40 µg/µL of aflibercept (Af), or 25 µg/µL of bevacizumab (Be), or 10 µg/µL of ranibizumab (Ra) were applied. Endothelin-1 (ET1), a potent vasoconstrictor, was used as a positive control, and phosphate-buffered saline (PBS) was used as a control. Results: For group S, no significant changes were observed after PBS (baseline, 1, 5, and 15 min: 46.3, 44.5, 44.8, and 43.2%), Be (46.1, 46.7, 46.7, and 46.3%), Ra (44.7, 45.0, 44.7, and 45.6%), and Af (46.5, 46.2, 45.9, and 46.1%, repeated ANOVA) were applied topically. Significant decreases in the VD were observed after ET1 (46.7, 28.1, 32.1, and 34.0%, p < 0.05) was topically applied. For group V, no significant differences were observed for all anti-VEGF agents. Conclusions: The topical application or intravitreal injections of anti-VEGF agents do not cause a change in the VD of the intestinal vessels, which may be related to its safety.

Effects of suspension of anti-vascular endothelial growth factor treatment for neovascular age-related macular degeneration in clinical setting.

PURPOSE: To investigate the outcomes of a suspension of anti-vascular endothelial growth factor (anti-VEGF) treatments in the eyes with neovascular age-related macular degeneration (nAMD). METHODS: This was a retrospective study that examined eyes having no exudation for 48 weeks while undergoing intravitreal anti-VEGF injections every 12 to 16 weeks. The rate and time of recurrences, best-corrected visual acuity (BCVA), central subfield thickness (CST), number of visits, and reactivity to anti-VEGF were determined after the suspension of the anti-VEGF treatments. RESULTS: In 34 eyes of 34 patients, 17 eyes (50.0%) had a recurrence during the 24-month follow-up period. The median time of a recurrence was 10 months. The BCVA was maintained for 24 months after the suspension regardless of the development of any recurrences. In 41.7% of the eyes that resumed treatment, the duration of exudation suppression by the anti-VEGF therapy was shorter than 12 weeks during the 12 months after restarting the anti-VEGF treatments. There was a significant increase in the number of visits during the first year after beginning the suspension versus during the 1 year before the suspension (non-recurrence group; P = 0.007, recurrence group; P = 0.001). CONCLUSION: Although one-half of the eyes had a recurrence within 24 months after a suspension of anti-VEGF treatment, the BCVA was maintained after a resumption of the anti-VEGF treatments. However, the number of hospital visits increases regardless of the recurrences and the lesion stability is altered by the anti-VEGF suspension. Clinicians should explain both the advantages and disadvantages of anti-VEGF suspension to nAMD patients.

Three cases of acute retinal necrosis with atypical fundus findings.

PURPOSE: To determine the mechanism for the development of segmental granular lesions along the retinal vessels in eyes with acute retinal necrosis (ARN). METHOD: This was a retrospective analysis of the medical records of 3 eyes of 3 patients who were diagnosed with ARN that had atypical segmental granular lesions aligned along the retinal vessels. RESULTS: The segmental granular lesions were present on both the retinal arteries and veins throughout the retina. Optical coherence tomography (OCT) showed that the granular lesions protruded into the vitreous cavity. Histopathological examinations confirmed that the lesions were made up of lymphocytes. CONCLUSIONS: We suggest that the granular lesions were formed by a mechanism similar to that of HTLV-1-associated uveitis (HAU). We also found that the granular lesions disappeared soon after vitrectomy.

Effects of Intravitreal Aflibercept on Retinal Function and Improvement of Macular Edema Associated With Diabetic Retinopathy.

Purpose: To determine the effectiveness of intravitreal aflibercept (IVA) on the retinal function in eyes with diabetic macular edema (DME). Methods: Twenty-five eyes of 25 patients with DME were treated with three consecutive monthly IVA injections. The retinal sensitivities (RS) within the central 10° were determined by microperimetry (MP). The central subfield macular thickness (CMT) was determined by optical coherence tomography, and the implicit times (IT) and amplitudes (Amp) of the flicker electroretinograms (ERGs) were determined from the ERGs elicited and recorded by the RETeval. The number of microaneurysms (MAs) was counted in the fundus photographs. The assessments were made before the IVA injections (pre-IVA) and one week after the IVA injections (post-IVA). The correlations between the reduction ratio of the MA numbers/CMT and RS/IT/Amp were evaluated. Results: The mean RS improved from 19.9 ± 5.9 dB to 22.0 ± 5.8dB, the CMT decreased from 485.7 ± 90.6 µm to 376.9 ± 81.6 µm, and the number of MAs decreased from 49.6 ± 33.2 to 24.8 ± 18.1 after the IVA injection (all P < 0.01). The changes in the IT from 31.3 ± 3.3 ms to 31.5 ± 3.1 ms and the Amp from 12.2 ± 5.5 µV to 11.3 ± 6.1µV post-IVA were not significant. A significant correlation was found between the relative changes in the CMT and RS (r = -0.43; P = 0.02), the MAs and RS (r = -0.38; P = 0.03). No significant correlation was observed between the relative changes of the number of MAs/CMT and IT/Amp. Conclusions: IVA can improve both central retinal function and anatomical conformation. Translational Relevance: A new aspect of aflibercept will be useful for DME treatment.

Comparison of 2-Year Outcomes between Intravitreal Ranibizumab and Intravitreal Aflibercept for Diabetic Macular Edema with "Treat-and-Extend" Regimen-Its Usefulness and Problems.

BACKGROUND: To compare the effectiveness of intravitreal ranibizumab (IVR) and intravitreal aflibercept (IVA) performed with the treat-and-extend (TAE) regimen on eyes with diabetic macular edema (DME). PATIENTS AND METHODS: This is a retrospective study of 125 eyes of 125 treatment-naïve DME patients who received anti-VEGF injections at three consecutive monthly intervals as the loading phase. The changes in the best-corrected visual acuity (BCVA), central retinal thickness (CRT), diabetic retinopathy severity scale (DRSS), and total injection numbers were compared between the two anti-VEGF agents. RESULTS: Among 125 eyes, 26 eyes completed the treatment with the TAE regimen for 24 months (20.8%). Thirteen eyes of 13 patients (mean age, 70.9 ± 6.0 years) received intravitreal injections of 0.5 mg ranibizumab, and 13 eyes of 13 patients (65.9 ± 8.6 years) received 2 mg aflibercept. No significant differences were detected in the baseline demographics. At 24 months, BCVA was significantly improved in both groups; from 0.31 ± 0.19 to 0.10 ± 0.12 logMAR units for IVR and 0.41 ± 0.19 to 0.16 ± 0.28 logMAR units for IVA (p = 1.29 × 10-9). CRT was significantly reduced in both groups; 440.9 ± 69.3 to 307.5 ± 66.4 µm for IVR and 473.9 ± 71.5 to 317.8 ± 71.2 µm for IVA (p = 3.55 × 10-9). No significant differences were detected in the improvements of BCVA, CRT in both groups, and the total injection numbers for 24 months (11.0 ± 1.2 for the IVA group and 12.0 ± 1.0 the IVR group). DRSS was significantly improved in both groups (p = 0.0004 for IVR and p = 0.009 for IVA). CONCLUSION: No significant differences were detected in the improvements of BCVA or CRT and injection numbers between the IVR and IVA groups treated with the TAE regimen. These results indicate that the results of the treatment with both agents with the TAE regimen were equally effective, but only 20.8% of patients completed 24 months of continuous treatment with the TAE regimen. Synopsis: There are no significant differences regarding effectiveness between the IVR and IVA groups treated with the TAE regimen for DME eyes.

Comparisons of Effective Fields of Two Ultra-Widefield Ophthalmoscopes, Optos 200Tx and Clarus 500.

PURPOSE: To compare the effective fields of the Optos 200Tx® and Clarus 500™, two ultra-widefield ophthalmoscopes, based on their ability to image branches of retinal vessel in the four retinal quadrants. METHODS: Ninety retinal images from 90 patients with various eye diseases were studied. All patients had undergone 200° retinal imaging to obtain a single image of Optos (O) and the montage of two images of the Clarus (C). The highest number of traceable vessel branches in the four retinal quadrants was determined by two masked raters. An image was classified as "O > C" when the number of identifiable branch was greater in the Optos than the Clarus, as "O = C" when the number was equal and as "O < C" when the number was fewer in the Optos than the Clarus. RESULTS: The appearance probability of "O > C" was significantly higher at the upper temporal quadrant than "O < C" (p < 0.01 for both raters). In contrast, the appearance probability of "O < C" was significantly higher at the lower nasal quadrant than "O > C" (p < 0.01 for both raters). There were no significant differences in the appearance probability between "O > C" and "O < C" at the other two retinal quadrants (p > 0.50 for both raters). CONCLUSIONS: These results demonstrate that the effective field of views was different between the two devices at different retina quadrants. Further studies are needed to clarify possible factors such as artifacts by the eyelashes, differences in the depth of focus, motion of the device, and different locations of the images on the effective field of views.

Two year result of intravitreal bevacizumab for diabetic macular edema using treat and extend protocol.

To determine the efficacy of the treat and extend (TAE) protocol with intravitreal bevacizumab (IVB) for managing diabetic macular edema (DME).Retrospective, single-center study.For this retrospective study, 42 eyes of 42 patients were initially treated with 3 consecutive monthly IVB injections (loading phase), after which they were selected for different additional therapies. For the TAE protocol, the baseline treatment interval was selected to be 8 weeks and was sequentially lengthened by 2 weeks if the central macular thickness (CMT) was <300 µm at 2 consecutive examinations.Among the 42 eyes, 8 eyes (19.0%) received the TAE treatment for 2 years. The BCVA was improved significantly from 0.37 ±â€Š0.04 before treatment to 0.19 ±â€Š0.04 logMAR units at 2 years after the TAE determined IVB injections (P < .05). The ratio of eyes with a gain of the BCVA by more than 2 lines was 37.5%. The CMT was significantly reduced from 515.4 ±â€Š75.5 to 303.6 ±â€Š45.0 µm after 2 years (P < .01). The mean number of TAE injection was 8.8 and the mean injection interval was 11.0 weeks.After the loading phase, 19.0% of patients can be treated with the TAE protocol. Although significant visual improvements were obtained after the TAE protocol, it does not apply to every DME case.

[Intravitreal Triamcinolone Acetonide for Persistent Diabetic Macular Edema after Vitrectomy].

PURPOSE: To determine whether intravitreal triamcinolone acetonide (IVTA) is effective in resolving edema in eyes with persistent diabetic macular edema (DME) after vitrectomy. PATIENTS AND METHODS: Sixteen eyes of 16 patients were given 4 mg IVTA after vitrectomy for DME. The best-corrected visual acuity (BCVA), central macular thickness (CMT), and average threshold (AT) of the central retina were determined during the 24 weeks follow-up period. Patients were divided into two groups; early treatment group and late treatment group. RESULTS: The BCVA was significantly improved at 12 weeks, the CMT was significantly improved at 24 weeks, and the AT was significantly improved at 4 weeks after IVTA (repeated ANOVA, p < 0.05). The BCVA was more significantly improved in the early treatment group than in the late treatment group at 4 and 12 weeks (unpaired t test, p < 0.05). CONCLUSION: Our results indicate that IVTA should be considered as treatment for patients with persistent DME after vitrectomy, especially with early treatment patients.

Importance of Central Retinal Sensitivity for Prediction of Visual Acuity after Intravitreal Bevacizumb in Eyes with Macular Edema Associated with Branch Retinal Vein Occlusion.

OBJECTIVE: To determine whether the baseline retinal sensitivity can predict the best-corrected visual acuity (BCVA) at 1 month after intravitreal bevacizumab (IVB) in eyes with macular edema (ME) associated with a branch retinal vein occlusion (BRVO). SUBJECTS AND METHODS: We evaluated 16 eyes of 16 patients who had ME associated with a BRVO. The mean ± standard deviation age was 69.1 ± 8.9 years, and all had a single IVB injection. The BCVA, central macular thickness (CMT), integrity of the ellipsoid zone (EZ) of the photoreceptors, and retinal sensitivity were determined before (baseline) and at 1 day, 1 week, and 1 month following the IVB. The average threshold retinal sensitivity (AT) within the central 10° was determined by Macular Integrity Assessment. The correlations between the BCVA at 1 month and the CMT, integrity of the EZ, and AT at each visit were determined. RESULTS: One month after IVB, the BCVA improved significantly from 0.56 ± 0.27 logMAR units to 0.32 ± 0.28 logMAR units, and the CMT from 611.4 ± 209.3 µm to 258.7 ± 64.0 µm (P <0.05). The AT improved significantly from 17.9 ± 5.3 dB to 21.2 ± 5.0 dB (P <0.05). At 1 day after the treatment, both the integrity of the EZ (r = 0.59) and the retinal sensitivity (r = 0.76) were moderately correlated with the BCVA at 1 month. CONCLUSION: These results indicate that both the integrity of the EZ and the AT at 1 day after the IVB can predict the BCVA after treatment for ME associated with BRVO. There is a possibility that these parameters will predict the effectiveness of IVB for each case.

Short Pulse Duration High-Power Laser Photocoagulation during Vitrectomy for Diabetic Retinopathy Reduces Postoperative Inflammation.

The aim of this preliminary study was to determine the effectiveness of short pulse duration, high-power laser photocoagulation (PC) during vitrectomy for diabetic retinopathy (DR).The effects of short pulse duration PC with power of 340-360 mW and duration of 0.02 second were compared to conventional PC with power of 120-150 mW and duration of 0.2 second. The degree of inflammation was quantified by laser flare cell photometry before and at 1 day, 1 week, 4 week, and 12 weeks postoperatively. Twenty-two eyes of 22 consecutive patients were studied. Ten eyes were treated with short pulse duration PC and 12 eyes with conventional PC. The total energy was significantly lower in the short pulse duration PC group than in the conventional PC group (P = 0.007). The flare cell values were not significantly different between the two groups after 1 day, but at 1 week, the flare cell value was significantly lower in the short pulse duration PC group than in the conventional PC group (P = 0.04). This difference was also present at 4 and 12 weeks (P<0.05). The significant lower inflammation after short pulse duration PC than conventional PC indicates that the short pulse duration PC protocol should be considered to treat DR.