Subjective Symptoms of First-Time Wearers of Verofilcon A Silicone Hydrogel One-Day Disposable Contact Lenses: A First Time Use of Verofilcon A (FTVeA) Study.

Purpose: Verofilcon A, a new daily disposable silicone hydrogel soft contact lens (SCL), is expected to be more comfortable to wear due to its smooth surface. This study aims to compare the comfort level of verofilcon A with eyeglasses in first-time SCL wearers. Methods: A total of 58 new SCL wearers participated in this study. Participants' comfort scores while wearing glasses or verofilcon A were examined at baseline (glasses) and one and four weeks after starting to wear the SCLs. Results: At the end of the one-month study period, no participants had abandoned wearing the SCLs due to discomfort. The vision scores (1-10) for glasses (baseline) and SCLs (week one, week four) were better with SCLs than glasses in the morning (7.9 ± 1.9 vs 8.9 ± 1.3, 9.0 ± 1.2, p<0.01), during the day (8.0 ± 1.6 vs 9.0 ± 1.1, 8.9 ± 1.2, p<0.01), at the end of the day (7.2 ± 2.1 vs 8.5 ± 1.5, 8.7 ± 1.4, p<0.01), and the entire day (7.7 ± 1.7 vs 8.9 ± 1.2, 8.7 ± 1.3, p<0.01). The percentages of participants who agreed that wearing SCLs at week four was as good as or better than glasses in terms of overall vision, peripheral vision, vision at the end of the day, comfort during the day, comfort at the end of the day, less fatigue during the day, and less fatigue at the end of the day were 91.4%, 100.0%, 91.4%, 89.7%, 82.8%, 87.9%, and 89.7%, respectively. Of the participants, 93.1%, 100.0%, and 93.1% felt that the SCLs were easy to wear, more comfortable than expected, and would like to purchase the same lenses in the future, respectively. Conclusion: These findings suggest that verofilcon A is more comfortable than glasses and is effective as an introductory lens for first-time SCL wearers.

Visual Acuity and Retinal Thickness and Sensitivity after Intravitreal Ranibizumab Injection for Macular Edema in Branch Retinal Vein Occlusion.

Background/Objectives: To investigate changes in visual acuity and retinal sensitivity and thickness after intravitreal ranibizumab injection (IRI) for macular edema in branch retinal vein occlusion (BRVO) patients. Methods: This study evaluated 34 patients with treatment-naïve BRVO and at least 6 months' follow-up after pro re nata IRI. Best-corrected visual acuity (BCVA) was determined as the logarithm of the minimum angle of resolution (logMAR). In nine retinal regions, retinal sensitivity was calculated by MP-3 microperimetry; and in nine macular subfields, retinal thickness was measured by optical coherence tomography (OCT); evaluations were performed before IRI and then monthly for 6 months. Results: IRI significantly improved visual acuity and retinal sensitivity and thickness. In patients with good improvement in BCVA (change in logMAR > 0.2), IRI significantly improved retinal sensitivity in eight of nine regions, i.e., in all except the outer non-occluded region, and in patients with poor improvement in BCVA (change in logMAR < 0.2), in six of nine regions, i.e., not in the inner, outer non-occluded, and outer temporal regions. We found significant differences in the trend profile in the foveal, outer occluded, and inner nasal regions between patients with good and poor improvement in BCVA. Conclusions: The findings suggest that IRI improves visual acuity and retinal sensitivity and thickness and that retinal effects may vary between patients with good and poor visual improvement.

Comparison of comfort and tear stability with two novel silicone-hydrogel daily disposable contact lenses.

BACKGROUND: The surface wettability of soft contact lenses (SCLs) affects the wearing comfort. Verofilcon A is a daily disposable silicone hydrogel contact lens with SMARTSURFACE® technology, ensuring high surface wettability. PURPOSE: To evaluate tear stability on the surface of verofilcon A and narafilcon A SCLs and correlate these findings with clinical parameters and patients' discomfort. METHODS: Sixty-two SCL wearers (124 eyes) with SCL discomfort were randomly assigned to use narafilcon A (control SCL) and verofilcon A for 2 weeks each by crossover. The noninvasive tear break-up time (NIBUT) of the naked eye at baseline and pre-lens NIBUT (PL-NIBUT) of the SCL surface after 2 weeks of using each SCL were measured using the DR-1α® dry eye observation device. Corneal superficial punctate keratopathy (SPK) (0-3) and conjunctival hyperemia (0-3), and comfort level of SCL wear (1-10) were also evaluated. RESULTS: NIBUT and PL-NIBUT values were 4.6 ± 2.3 s for the naked eye, 6.6 ± 6.6 s for narafilcon A, and 11.3 ± 3.5 s for verofilcon A. verofilcon A had significantly higher PL-NIBUT than the naked eye and narafilcon A (p < 0.05). SPK (0.16 ± 0.48 vs. 0.00 ± 0.00, p < 0.01) and conjunctival hyperemia (1.15 ± 0.82 vs. 0.49 ± 0.50, p < 0.01) scores were lower when wearing verofilcon A than narafilcon A. The ocular comfort score of wearing SCLs was higher with verofilcon A than with narafilcon A (8.7 ± 1.8 vs. 9.8 ± 0.5, p < 0.01). The ocular comfort score for wearing verofilcon A was higher, regardless of the baseline NIBUT. CONCLUSION: The results of this study showed a consistent surface-wetting advantage of verofilcon A in patients with ocular discomfort. verofilcon A was used comfortably in patients with low NIBUT scores at baseline. The findings suggest that verofilcon A is recommended for SCL wearers experiencing SCL-related dry eye symptoms and discomfort.

Patient Satisfaction and Tear Film Break-Up Time After First-Time Wearing of Silicone Hydrogel Contact Lenses.

PURPOSE: The dryness and discomfort associated with soft contact lenses (SCLs) prevent their continued use. Recently, verofilcon A, a new daily disposable silicone hydrogel material SCL, was introduced, which has a high water content (surface water content of 80% or more) that overcomes the low water content drawback of silicone hydrogels. In this study, we evaluated the non-invasive tear break-up time (NIBUT) and comfort level in individuals wearing verofilcon A SCL for the first time. METHODS: We enrolled 42 first-time SCL wearers, comprising 84 eyes. NIBUT was measured using the DR-1α® dry eye observation device at the state of the naked eye before SCL wear (baseline) and at one and four weeks after the first SCL wear. Additionally, we conducted a questionnaire survey during the fourth week to assess the comfort level (0-10) of SCL wear. Results: The NIBUT values were significantly higher at one week (10.8 ± 2.2 s, p<0.01) and four weeks (11.4 ± 2.2 s, p<0.01) after the first SCL wear than those at baseline (5.9 ± 2.0 s). Comfort level in SCL use was significantly higher at one week (9.0 ± 1.1, p<0.01) and four weeks (8.7 ± 1.2, p<0.01) than that at baseline (7.8 ± 1.8), and this level was higher regardless of the baseline NIBUT value. CONCLUSION: Prolonged BUT and increased comfort levels were observed in individuals wearing verofilcon A SCLs. Improvement in tear fluid retention was found to alleviate dry eye and discomfort, suggesting that verofilcon A may be a beneficial introductory lens for first-time SCL wearers.

Anti-Vascular Endothelial Growth Factor Therapy with or Without Initial Steroid Therapy for Macular Edema in Branch Retinal Vein Occlusion.

Purpose: In branch retinal vein occlusion (BRVO), administering steroid injections to inhibit expression of inflammatory factors in the first phase of macular edema may reduce recurrence of the edema. The purpose of our study was to investigate the functional and morphological prognosis and frequency of recurrence after injection of an anti-vascular endothelial growth factor (VEGF) with and without initial steroid therapy to treat macular edema with BRVO. Patients and Methods: Patients with BRVO and macular edema (41 eyes) received intravitreal ranibizumab injection (IRI) alone (IRI group, 21 eyes) or subtenon triamcinolone (STTA) injection and IRI (combination group, 20 eyes). Patients in both groups with recurrent macular edema received further IRI as appropriate. A laser flare meter was used to assess aqueous flare values, and an optical coherence tomography device was used to measure central macular thickness (CMT). Before the first treatment, we obtained samples of aqueous humor and analyzed them by the suspension array method to evaluate VEGF, placental growth factor (PlGF), platelet-derived growth factor (PDGF)-AA, soluble intercellular adhesion molecule (sICAM)-1, monocyte chemoattractant protein 1 (MCP-1), interleukin (IL)-6, IL-8, and interferon-inducible 10-kDa protein (IP-10). Results: The two groups were not significantly different with regard to levels of VEGF, PlGF, PDGF-AA, sICAM-1, MCP-1, IL-6, IL-8, or IP-10. Best-corrected visual acuity, CMT, and aqueous flare value (IRI group, baseline 8.69 ± 4.55 photon counts/ms; combination group, baseline 9.21 ± 3.72 photon counts/ms) improved significantly in both groups without significant intergroup differences. Analyses showed no significant intergroup differences in the mean number of IRIs during the 12-month follow-up, but the proportion of patients without recurrence (ie, who received only one IRI) was significantly higher in the combination group than in the IRI group (P = 0.032). Furthermore, the time to initial recurrence was significantly longer in the combination group than in the IRI group (P = 0.003). Conclusion: These findings suggest that initial STTA injection and IRI may have a synergistic effect in patients with BRVO and macular edema in that they increase the time between anti-VEGF treatments.

Effects of Intravitreal Ranibizumab Injection to Treat Macular Edema due to Central Retinal Vein Occlusion on Choroidal Findings and Functional-Morphological Parameters.

INTRODUCTION: Little research has examined the effects of anti-vascular endothelial growth factor therapy on subfoveal choroidal thickness (SCT), choroidal blood flow, aqueous flare, and humor levels of growth and inflammatory factors in patients with macular edema due to central retinal vein occlusion (CRVO). METHODS: In 58 patients with macular edema due to CRVO treated by intravitreal ranibizumab injection (IRI), we retrospectively assessed best-corrected visual acuity (BCVA, assessed as the logarithm of the minimum angle of resolution [logMAR]), 8 aqueous factors (by suspension array), mean blur rate (MBR; estimated by laser speckle flowgraphy as a measure of choroidal blood flow), aqueous flare (with a laser flare meter), and SCT and central macular thickness (CMT; by optical coherence tomography). RESULTS: After 4 weeks, IRI resulted in a significant improvement in BCVA and CMT and a significant reduction in SCT, choroidal MBR, and aqueous flare. SCT was significantly positively correlated with placental growth factor and significantly negatively correlated with platelet-derived growth factor-AA, and change in SCT was significantly negatively correlated with change in BCVA (logMAR). Aqueous flare was significantly negatively correlated with SCT. CONCLUSION: Growth and inflammatory factors may be associated with SCT, and changes in SCT may be associated with changes in BCVA after IRI to treat macular edema due to CRVO.

Effects of Intravitreal Ranibizumab Injection on Peripheral Retinal Microcirculation and Cytokines in Branch Retinal Vein Occlusion with Macular Edema.

Background and Objectives: To investigate peripheral blood flow in retinal vessels and vessel diameters after intravitreal ranibizumab injection (IRI) and the relationship between these parameters and cytokines in branch retinal vein occlusion (BRVO) with macular edema. Materials and Methods: We assessed relative flow volume (RFV) and the width of the main and branch retinal arteries and veins in the occluded and non-occluded regions before and after IRI in 37 patients with BRVO and macular edema. Measurements were made using laser speckle flowgraphy (LSFG). When performing IRI, we obtained samples of aqueous humor and analyzed them using the suspension array method to evaluate vascular endothelial growth factor (VEGF), placental growth factor (PlGF), platelet-derived growth factor (PDGF)-AA, soluble intercellular adhesion molecule (sICAM)-1, monocyte chemoattractant protein 1 (MCP-1), interleukin (IL)-6, IL-8, and interferon-inducible 10-kDa protein (IP-10). Results: In both retinal regions, before and after IRI, the RFV in the main artery and vein showed a significant correlation with the summed RFV in the respective branch vessels 1 and 2. In the occluded region, the RFV in the main vein was significantly negatively correlated with MCP-1, PDGF-AA, IL-6, and IL-8; the RFV in branch vein 1 was significantly negatively correlated with PlGF, MCP-1, IL-6, and IL-8; PDGF-AA was significantly negatively correlated with the width of the main and branch veins; and the RFVs of the main artery and vein decreased significantly from before to 1 month after IRI. Conclusions: Contrary to expectations, the study found that anti-VEGF therapy does not affect RFV in arteries and veins in patients with BRVO and macular edema. Furthermore, retinal blood flow is poor in patients with high MCP-1, IL-6, and IL-8. Finally, high PDGF-AA may result in smaller venous diameters and reduced retinal blood flow.

New individualized aflibercept treatment protocol for branch retinal vein occlusion with macular edema.

We evaluated the long-term (24-month) efficacy of a novel individualized treatment protocol with 2 mg aflibercept for treatment-naive BRVO with macular edema. Each patient received an initial aflibercept injection and was then examined every 2 weeks until recurrence of edema. At recurrence, each patient received a second injection of aflibercept. The period of efficacy was defined as the time between the first and second injections. Subsequently, each patient was examined and re-injected with aflibercept at their personalized treatment interval, which was defined as 1 week shorter than the period of efficacy. Thirty-seven eyes of 48 patients showed recurrence after the initial injection. The mean period of efficacy was 92.5 ± 40.8 days, and the mean number of visits before recurrence, 7.6 ± 2.9. The mean 24-month best corrected visual acuity (BCVA) was significantly better than the mean baseline BCVA but significantly worse than the best BCVA during the period of efficacy. The mean gain of BCVA at 24 months was 0.07 ± 0.18 logMAR. The mean 24-month central macular thickness (CMT) was significantly lower than the mean baseline CMT but showed no difference from the mean best CMT (p = 0.060). The mean total number of visits during the 24 months was 15.8 ± 3.4. We conclude that the individualized treatment protocol that was based on the period of efficacy in treatment-naïve BRVO eyes with macular edema achieved satisfactory long-term visual outcome.

Role of Novel Inflammatory Factors in Central Retinal Vein Occlusion with Macular Edema.

Background and Objectives: To investigate associations among the aqueous humor levels of novel inflammatory factors, including FMS-related tyrosine kinase 3 ligand (Flt-3L), fractalkine, CXC chemokine ligand 16 (CXCL-16), and endocan-1; the severity of macular edema in central retinal vein occlusion (CRVO); and the prognosis of CRVO with macular edema after antivascular endothelial growth factor (VEGF) therapy. Materials and Methods: Aqueous humor was obtained during anti-VEGF treatment with intravitreal ranibizumab injection (IRI) in patients with CRVO and macular edema (n = 19) and during cataract surgery in patients with cataracts (controls, n = 20), and the levels of VEGF and novel inflammatory factors were measured. Macular edema was evaluated by central macular thickness (CMT) and neurosensory retinal thickness (TNeuro), and improvement was evaluated by calculating the percentage change in CMT and TNeuro from before to 1 month after IRI. Results: The levels of VEGF and the novel inflammatory factors were significantly higher in the CRVO group, and the levels of Flt-3L, CXCL-16, and endocan-1 were significantly correlated with each other and with the aqueous flare value. Baseline levels of Flt-3L, CXCL-16, and endocan-1 had a significantly negative correlation with the change in CMT, and the baseline level of CXCL-16 was significantly negatively correlated with the change in TNeuro. Conclusions: Relations among novel inflammatory factors should be further investigated. These findings may help improve understanding of macular edema in CRVO patients and aid the development of new treatments targeting novel inflammatory factors.

Impact of the COVID-19 Pandemic on Anti-Vascular Endothelial Growth Factor Therapy for Diabetic Macular Edema in Japan.

Anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME) improves visual acuity. However, repeated injections during routine outpatient visits are required to maintain this effect. The recent sudden global outbreak of coronavirus disease 2019 (COVID-19) had a major impact on daily life, including medical care, such as the provision of VEGF therapy. We retrospectively investigated the relationship between the number of anti-VEGF injections for DME and the number of new COVID-19-positive patients at 23 centers in Japan. We also surveyed ophthalmologists regarding the impact of the COVID-19 pandemic on anti-VEGF therapy. In the third and fourth waves of the pandemic, when the number of infected patients increased, the number of injections significantly decreased. In the first, third, and fourth waves, the number of injections increased significantly during the last month of each wave. Approximately 60.9% of ophthalmologists reported that the number of injections decreased after the pandemic. Of the facilities, 52.2% extended the clinic visit intervals; however, there was no significant difference in the actual number of injections given between before and after the pandemic. Although the number of injections temporarily decreased, Japanese ophthalmologists maintained the total annual number of anti-VEGF injections for DME during the pandemic.

Intravitreal ranibizumab improves macular sensitivity in patients with central retinal vein occlusion and macula edema.

BACKGROUND: Patients with central retinal vein occlusion (CRVO) and macular edema often are treated by intravitreal ranibizumab injection (IRI). The role of changes in macular sensitivity in the positive effects of IRI on visual functions is unclear. Therefore, we assessed the relationship between macular sensitivity and improvement of visual functions. METHODS: We included 15 eyes of 15 patients with treatment-naïve CRVO and followed patients for 6 months after pro re nata IRI. IRI was repeated if the central macular thickness was greater than or equal to 300 µm. Microperimetry-3 was used to measure macular sensitivity within the central 1-mm, 3-mm, and 6-mm fields before and monthly for 6 months after IRI. RESULTS: IRI significantly improved mean macular sensitivity over time within the central 1-mm, 3-mm, and 6-mm fields (all P < 0.001). None of the fields showed significant differences in the change of mean macular sensitivity between patients with little improvement in best corrected visual acuity (BCVA; i.e., in patients with a change in logarithm of the minimum angle of resolution [logMAR] BCVA < 0.3) and those with marked improvement in BCVA (change in logMAR BCVA > 0.3). The mean macular sensitivity before IRI showed correlations with the improvement of macular sensitivity in every field. CONCLUSION: These findings suggest that IRI improves macular sensitivity in patients with CRVO and macular edema independent of any improvement in BCVA and that macular sensitivity before treatment is associated with improvement of macular sensitivity after treatment.

RELATIONSHIP BETWEEN CHOROIDAL FINDINGS AND GROWTH FACTORS, CYTOKINES, AND OTHER INFLAMMATORY MEDIATORS AFTER INTRAVITREAL RANIBIZUMAB INJECTION IN PATIENTS WITH MACULAR EDEMA SECONDARY TO BRANCH RETINAL VEIN OCCLUSION.

PURPOSE: To examine possible associations between subfoveal choroidal thickness (SCT), choroidal blood flow, aqueous flare value, and aqueous humor levels of multiple growth factors, cytokines, and other inflammatory mediators in patients with branch retinal vein occlusion and macular edema who received antivascular endothelial growth factor (anti-VEGF) therapy. METHODS: We recruited 65 patients with macular edema due to branch retinal vein occlusion who received intravitreal ranibizumab injection and measured aqueous levels of eight factors by the suspension array method. Furthermore, we evaluated choroidal blood flows by laser speckle flowgraphy and quantified them as the mean blur rate and measured aqueous flare values using a laser flare meter and SCT and central macular thickness by optical coherence tomography. RESULTS: At 1 month after intravitreal ranibizumab injection, central macular thickness was significantly improved and SCT, choroidal mean blur rate, and aqueous flare value were significantly decreased. SCT was significantly correlated with vascular endothelial growth factor and placental growth factor, and the change in both SCT and central macular thickness was significantly correlated with the change in aqueous flare value. However, only SCT was significantly negatively correlated with the aqueous flare value. CONCLUSION: Growth factors seem to play a role in SCT. In macular edema with branch retinal vein occlusion, antivascular endothelial growth factor agents may decrease SCT by reducing inflammation.

Background Factors Affecting Visual Acuity at Initial Visit in Eyes with Central Retinal Vein Occlusion: Multicenter Study in Japan.

PURPOSE: To determine the baseline characteristics of patients with central retinal vein occlusion (CRVO) that were significantly associated with the best-corrected visual acuity (BCVA) at the initial examination. METHODS: This was a retrospective multicenter study using the medical records registered in 17 ophthalmological institutions in Japan. Patients with untreated CRVO (≥20-years-of-age) who were initially examined between January 2013 and December 2017 were studied. The patients' baseline factors that were significantly associated with the BCVA at the initial examination were determined by univariate and multivariate linear regression analyses. RESULTS: Data from 517 eyes of 517 patients were analyzed. Univariate analyses showed that an older age (r = 0.194, p < 0.001) and the right eye (r = -0.103, p < 0.019) were significantly associated with poorer BCVA at the initial visit. Multivariate analyses also showed that an older age (ß = 0.191, p < 0.001) and the right eye (ß = -0.089, p = 0.041) were significantly associated with poorer BCVA at the initial visit. CONCLUSIONS: The results indicate that an older age, a known strong factor, and the right eye were significantly associated with poorer BCVA at the initial visit to the hospital. These results suggest that functional and/or anatomical differences between the right and left eyes may be involved in these results.

The Impact of Interval between Recurrence and Reinjection in Anti-VEGF Therapy for Diabetic Macular Edema in Pro Re Nata Regimen.

BACKGROUND: Pro re nata (PRN) regimen using anti-vascular endothelial growth factor (VEGF) agent is popular for the treatment of diabetic macular edema (DME). We investigated the influence of waiting time (WT) and interval between the date of recurrence of edema and re-injection on treatment efficacy. METHODS: This retrospective study conducted at 7 sites in Japan enrolled patients who received intravitreal injection of ranibizumab (IVR) and aflibercept (IVA) in 1+PRN regimen. Enrolled patients were divided into 2 groups: prompt group (less than 1 week) and deferred group (3 weeks or more). Central retinal thickness (CRT) and best corrected visual acuity (BCVA) were measured every month for 1 year. RESULTS: CRT in the deferred group was significantly higher than that in the prompt group at 2, 5, 6, 7, and 12 months (p < 0.05). BCVA in the prompt group was significantly better than that in the deferred group at 7, 10, and 12 months (p < 0.05). CONCLUSION: The prompt group was superior in anatomical and functional improvement of DME in anti-VEGF therapy than the deferred group. Our data suggests that shorter WT is recommended for better visual prognosis in the treatment for DME.

Retinal Blood Flow as a Predictor of Recurrence of Macular Edema after Intravitreal Ranibizumab Injection in Central Retinal Vein Occlusion.

INTRODUCTION: To investigate the relationship between retinal blood flow and the presence or absence of macular edema (ME) recurrence after intravitreal ranibizumab injection (IRI) in patients with central retinal vein occlusion (CRVO). METHODS: We reviewed the medical records of 16 eyes with ME associated with CRVO. All eyes had received pro re nata IRI. Repeat IRI was performed if the central macular thickness was ≥300 µm. At 12 months, patients without additional IRI in the past 6 months were assigned to the resolved group, and those with additional IRI, to the recurrence group. We used laser speckle flowgraphy (LSFG) to measure the mean blur rate (MBR) of the optic disc before and after IRI. RESULTS: Ten of the 16 eyes were assigned to the resolved group, and the other 6 eyes to the recurrence group. At several visits in the 12 months after IRI, MBR was significantly higher in the resolved group than in the recurrence group. Percent change of MBR (%Δ MBR) from baseline was significantly higher in the resolved group than in the recurrence group at 1 month (initial %Δ MBR) and 11 and 12 months. Multivariate stepwise analysis showed that the initial %Δ MBR was significantly and negatively correlated with the number of IRIs. DISCUSSION/CONCLUSION: These findings suggest that determining %Δ MBR in LSFG may be a useful way to determine the likelihood of ME recurrence in CRVO patients.

Role of ICAM-1 in impaired retinal circulation in rhegmatogenous retinal detachment.

Many studies have demonstrated that rhegmatogenous retinal detachment (RRD) leads to impaired retinal circulation. However, the involvement of inflammation in the RRD-induced worsening of retinal circulation was obscure. This retrospective observational study included 150 patients with primary RRD (macula-on, n = 63; macula-off, n = 87) who underwent 25-gauge microincision vitrectomy surgery (25G MIVS). Total retinal blood flow was represented by the mean blur rate (MBR) of the optic nerve head vessel, measured by laser speckle flowgraphy preoperatively and until 6 months postoperatively. Aqueous humor samples were obtained during surgery to determine cytokine concentrations by enzyme-linked immunosorbent assay. At 3 and 6 months postoperatively, there were no significant differences between eyes with macula-on RRD and fellow eyes. However, in macula-off RRD, MBR remained significantly lower in RRD eyes 6 months postoperatively (P < 0.05). Log-transformed levels of soluble intercellular adhesion molecule-1 (sICAM-1) were negatively correlated with relative MBR (r-MBR, RRD eye/fellow eye) before surgery (r = - 0.47, P = 0.01) in macula-on, but not macula-off, RRD. Six months postoperatively, r-MBR correlated significantly with sICAM-1 levels (r = - 0.36, P = 0.02) in macula-off RRD. ICAM-1 may play a role in RRD-induced deterioration of retinal circulation.

Involvement of Cytokines in the Pathogenesis of Diabetic Macular Edema.

Diabetic macular edema (DME) is a critical complication of diabetic retinopathy, a condition that arises from the breakdown of the blood-retinal barrier and the consequent increase in vascular permeability. Over the years, attempts have been made to treat DME by various approaches, including laser photocoagulation, steroid triamcinolone acetonide, and vitrectomy. However, treatment was unsatisfactory until research identified vascular endothelial growth factor (VEGF) as a factor in the pathogenesis of DME. Intraocular anti-VEGF agents show good efficacy in DME. Nevertheless, in some patients the condition recurs or becomes resistant to treatment, suggesting that other factors may be involved. Because inflammation and retinal hypoxia are seen in DME, research has examined the potential role of cytokines and other inflammatory mediators. In this review, we provide an overview of this research and describe feedback mechanisms that may represent a target for novel treatments.

Effects of ranibizumab on growth factors and mediators of inflammation in the aqueous humor of patients with diabetic macular edema.

PURPOSE: The study aims to investigate changes in the aqueous humor levels of 8 growth factors and inflammatory mediators after intravitreal ranibizumab injection (IRI) and the relationship between these substances and functional-morphological parameters in patients with diabetic macular edema (DME). METHODS: We recruited 25 patients with DME who were scheduled to receive 2 doses of IRI at monthly intervals. At baseline and 1 month after IRI, we measured aqueous levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), monocyte chemoattractant protein 1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1), platelet-derived growth factor (PDGF)-AA, interleukin (IL)-6, IL-8, and interferon-gamma inducible protein 10 (IP-10) by the suspension array method. Central macular edema (CMT) or macular volume (MV) was examined by optical coherence tomography before and 1 month after IRI, and the improvement of macular edema was evaluated by calculating the percent change of CMT or MV. RESULTS: Aqueous humor levels of VEGF, PlGF, PDGF-AA, and IP-10 were significantly decreased 1 month after IRI (P < 0.001, P = 0.002, P = 0.002, and P = 0.005, respectively). In addition, the baseline aqueous humor levels of PlGF, MCP-1, and IL-6 were significantly correlated with the improvement in best corrected visual acuity (P = 0.036, P = 0.024, and P = 0.049, respectively). The baseline aqueous humor level of sICAM-1 was significantly negatively correlated with the change in CMT (P = 0.005), and the baseline aqueous humor levels of VEGF and PlGF were significantly correlated with the change in MV (P = 0.020 and P = 0.003, respectively). Furthermore, the percentage reduction in VEGF after IRI was significantly correlated with the change in MV (P = 0.037). CONCLUSIONS: Our findings suggest that the change in aqueous humor levels of VEGF, PlGF, and ICAM-1 in DME may not only be an anatomic response but also a potential therapeutic target. CLINICAL TRIAL REGISTRATION: This study was registered in the University Hospital Medical Information Network (UMIN) clinical trial registry. The registration number is UMIN000030301.