Vitreous Reflux Research Articles

A proof-of-concept study of a prototype needle that mitigates intraocular pressure rise following intravitreal injection

PurposeTo determine the feasibility of a prototype needle that enhances vitreous reflux (VR) to control intraocular pressure (IOP) in intravitreal injection (IVI).MethodsWe created an eye model to compare IVI using a standard 30-G needle with four different versions of a 30-G prototype needle with one to four surface grooves that enhanced VR. We injected 50, 70, and 100 µl saline through porcine sclera or 460-µm-thick rubber and measured the peak and 3-second pressure before we extracted the needle and measured the 10-second pressure.Results50-µl injection through sclera with the standard needle resulted in mean (SD) pressure of 58.6 (3.8) mmHg at peak, 52.8 (4.7) mmHg at 3 s, and 39.6 (18.0) mmHg at 10 s. The prototype needle lowered the pressure; four grooves resulted in mean (SD) pressure of 29.4 (5.6) mmHg at peak, 22.0 (3.7) mmHg at 3 s, and 7.2 (6.6) mmHg at 10 s. 70-µl and 100-µl injections through sclera with the standard needle resulted in mean (SD) pressure of 68.8 (3.6) and 86.0 (6.0) mmHg at peak. Similar to 50-µl injection, the prototype needle lowered the pressure for 70-µl and 100-µl injections. At 10 s, we observed varying leakage at the injection site for sclera but not for rubber.ConclusionsThe study provides proof of concept for a needle design for which surface grooves enhance VR and counteract the effect of IVI on IOP. The safety and efficacy of the prototype needle must be studied further in a clinical trial.

Association Of Conjunctival Vitreous Reflux With Intraocular Pressure Spikes After Intravitreal Bevacizumab Injection

Objective: To evaluate the effect of conjunctival vitreous reflux on intraocular pressure immediately after intravitreal bevacizumab injection. Methods: A prospective interventional study was done at Benazir Bhutto Hospital, for 6 months from 13-01-2021 to 12-07-2021.Patients were selected through a non-probability consecutive sampling technique. A total of 88 eyes undergoing intravitreal bevacizumab were included in the study. IOP was checked before injection, immediately after injection, at 30 minutes and 60 minutes. The presence or absence of conjunctival reflux was noted. Data was analyzed to see the association of post-injection IOP and conjunctival reflux. Results: Those having conjunctival reflux positive had mean Intraocular pressure before intravitreal injection 13.14+2.569, the p-value was 0.0001. Immediately after injection at 0 minutes it was 27.95+3.988, and the p value was 0.0001. At 30 minutes, it was reduced to 21.58+2.814, the p-value was 0.0001, and at 60 minutes, the mean intraocular pressure was 17.26+1.853, and the p-value was 0.001. Those having conjunctival reflux negative had mean Intraocular pressure before intravitreal injection 13.44+2.981, p-value 0.0001. Immediately after injection at 0 minutes it was 33.69+5.608, and the p-value was 0.0001. At 30 minutes, it was reduced to 24.51+5.337, the p-value was 0.0001, and at 60 minutes, the mean intraocular pressure was 18.98+2.973, and the p-value was 0.001. Conclusion: Patients with vitreous reflux positive had less IOP elevation as compared to those with vitreous reflux negative. Keywords: Intravitreal bevacizumab injection, Intraocular pressure, conjunctival reflux.

Background diseases and the number of previous intravitreal aflibercept injections on immediate intraocular pressure increase and vitreous reflux rate in phakic eyes.

To evaluate the effect of background diseases and number of previous intravitreal aflibercept injections (IVAIs) on immediate intraocular pressure (IOP) increase and vitreous reflux (VR) rate and to evaluate the correlation of both age and axial length with immediate IOP increase and VR rate. This study included 105 patients with cystoid macular edema secondary to retinal vein occlusion, 35 patients with diabetic macular edema, 69 patients with neovascular age-related macular degeneration (nAMD), and 12 patients with myopic choroidal neovascularization, which underwent first-time IVAI. The correlation of immediate IOP increase and VR rates with the four background diseases was investigated. Moreover, the correlation of age with immediate IOP increase and VR rate as well as correlation of axial length with immediate IOP increase and VR rate were evaluated. Further, 54 patients with nAMD were treated with IVAI>10 times (multiple IVAIs). Moreover, the correlation of immediate IOP increase and VR rates with first-time and multiple IVAIs in nAMD was determined. The immediate IOP increase (P=0.16) and VR rates (P=0.50) were almost similar among the four background diseases. The immediate postinjection IOP and age, VR rate and age, immediate postinjection IOP and axial length, or VR rate and axial length were not correlated in the four background diseases. The immediate IOP increase (P=0.66) and VR rates (P=0.28) did not significantly differ between first-time and multiple IVAIs in nAMD. Background diseases and number of previous IVAIs have no effect on immediate IOP increase and VR rate. Further, age and axial length have no correlation on immediate IOP increase and VR rate.

Effect of Vitreous Reflux after Intravitreal Aflibercept Injection for Macular Edema with Branch Retinal Vein Occlusion: A Real-World Study.

This study aimed to evaluate the therapeutic effect of vitreous reflux (VR) after intravitreal aflibercept injection (IVAI) for macular edema (ME) following naïve branch retinal vein occlusion (BRVO). Eighty patients with ME following BRVO were divided into three groups according to the conjunctival bleb diameter after IVAI as follows: group A (no VR), group; B (<3 mm VR), and group C (>3 mm VR). Each patient received single IVAI. The treatment response was evaluated with the best-corrected visual acuity (BCVA) and optical coherence tomography measurements of the retinal foveal thickness (RFT) before treatment and 1 month after the first injection. RFT >375 μm was defined as recurrence and received additional IVAI. The recurrence rate of ME and total numbers of IVAI were investigated at 12 months. The BCVA values at 1 month were 0.17 ± 0.29 in group A (n = 41), 0.18 ± 0.17 in group B (n = 18), and 0.19 ± 0.26 in group C (n = 21). The RFT at 1 month were 270 ± 45 μm in group A, 279 ± 24 μm in group B, and 290 ± 43 μm in group C, respectively. ME recurred in 29 out of 41 patients in group A, 15 out of 18 in group B, and 14 out of 21 in group C. The total numbers of IVAI were 2.50 ± 1.24 in group A, 2.59 ± 1.06 in group B, and 2.29 ± 1.27 in group C, respectively. In the above mentioned comparisons, no significant differences were found following an IVAI (P > 0.05). VR after IVAI did not affect the therapeutic effect in patients with ME following BRVO. Thus, we do not need to pay excess attention to VR in the case of IVAI.

Noninvasive method to reduce vitreous reflux following intravitreal injection

Aim To investigate the role of pre-injection antiglaucoma medications as a noninvasive method to prevent reflux following intravitreal injection (IVI). Patients and methods This single-center prospective randomized study included patients who were planned to receive an IVI of anti-vascular endothelial growth factor ranibizumab 0.05 ml for macular edema for diabetic macular edema, branch retinal vein occlusion, or choroidal neovascular membrane. Patients were randomized into five groups: no intervention (group 1), pre-injection topical brimonidine (group 2), pre-injection oral acetazolamide (Diamox) (group 3), pre-injection topical brimonidine and oral Diamox (group 4), and pre-injection paracentesis (group 5). The primary outcomes were the occurrence and degree of reflux following IVI. In addition, the evaluation of conjunctival bleb estimated the degree of reflux. Patient self-rated pain and early complications were secondary outcome measures. Results A total of 150 eyes of 150 patients were included. Vitreous reflux occurred in 13 (43%), 14 (46.7%), 19 (63.3%), six (20.0%), and four (13.3%) eyes in groups 1–5, respectively (P&lt;0.001). Additionally, higher degrees of reflux were observed in group 1 compared with other groups. Discussion In our study, we raised the question of whether the intraocular pressure (IOP) before injection affects vitreous reflux. Therefore, we compared the effect of different antiglaucomatous medications on lowering the pre-injection IOP, and so decrease the vitreous reflux. We found that in both the paracentesis group and group of combined topical brimonidine and oral Diamox group, vitreous reflux rate is reduced significantly (P&lt;0.001) because in these two groups, the IOP just before the injection was the lowest. Unfortunately, we could not measure the IOP after paracentesis and before the injection to avoid any risk of endophthalmitis, but we consider the paracentesis as a gold standard group for lowering IOP, although it is an invasive procedure. Interestingly, the self-rated pain rate was the same in all groups. Conclusion Pre-injection topical brimonidine combined with oral Diamox may be an effective and noninvasive method to prevent/reduce vitreous reflux following IVI.

Effect of quadrant switch on ıntraocular pressure change in ıntravitreal aflibercept or ranibizumab ınjection applications.

To evaluate the effect of injection quadrant switch on the intraocular pressure (IOP) change in intravitreal aflibercept or ranibizumab applications. 123 eyes of 123 patients who received intravitreal injection (IVE) into the superotemporal quadrant at least 10 times for age-related macular degeneration or diabetic macular edema have been recruited. The demographic data, lens status, IOP values (preoperative, postoperative 0th min, and postoperative 30th min), and amount of vitreous reflux (VR) following IVE have been recorded. Next IVE application was performed into the inferotemporal quadrant of the patient, which had never been injected before. The mean IOP value at postoperative 0th min was 50.24 ± 7.66mmHg after injections into the superotemporal quadrant and was 34.85 ± 4.96mmHg after injections into the inferotemporal quadrant. No significant difference was observed between the preoperative and postoperative 30th min-IOP values (p > 0.05), while a significant difference was found between the postoperative 0th min-IOP values among quadrants (p < 0.001). VR was significantly higher in applications into the inferotemporal quadrant than those into the superotemporal quadrant (p < 0.001). One of the most principal factors affecting the postoperative short-term IOP increase is the amount of VR, and this amount decreases the IOP following an IVE. The high amount of VR produced in the quadrant where the injection was applied for the first time caused a low-level IOP, while the low amount of VR formed in the quadrant where the repeated injections were applied caused a higher IOP.

“The effect of two different intravitreal injection techniques on frequency of vitreous reflux and on treatment response in neovascular AMD patients”

To determine the effect of two distinct intravitreal injection (IVI) techniques on the frequency of vitreous reflux (VR) and on treatment response at cumulative dosages in neovascular age-related macular degeneration (nAMD) patients. Ninety-three eyes of 93 nAMD patients were included in the study. IVI was performed in 47 eyes using the straight technique (ST) and 46 eyes with the tunneled technique (TT). Patients received three loading doses of intravitreal bevacizumab, and substantial VR was noted for each IVI. Central (CMT), 1mm (MT1), and 3mm (MT3) macular thicknesses were measured before and after treatment. VR frequency and treatment response were compared in both groups, and correlation analysis was performed. Post-treatment VR was seen in 91 of 141 IVI with the ST and 33 of 138 IVI with the TT. The decrease in CMT, MT1, and MT3 after treatment with the ST was 121.4±92.5μm, 65.3±50.6μm, 28.8±30.8μm, respectively, and with the TT was 114.0±97.5μm, 67.8±72.6μm, and 27.1±31.4μm, respectively. The ST substantially increased the rate of VR compared to the TT (P<0.001), whereas the decrease in CMT, MT1, and MT3 did not vary significantly (P>0.05). There was no correlation between VR rate and decreases in CMT, MT1, or MT3 (P>0.05). According to our findings, the ST resulted in a higher frequency of VR than the TT, but VR did not affect the treatment response, despite multiple doses. Complication rates were negligible with both approaches. As a result, it appears that practitioners may use either IVI approach.

Self-sealing hyaluronic acid-coated 30-gauge intravitreal injection needles for preventing vitreous and drug reflux through needle passage

Self-sealing hyaluronic acid (HA)-coated self-sealing 30-gauge needles exhibiting instant leakage prevention of intravitreal humor and injected drug were developed in this study. Ninety New Zealand rabbits were used in this study. We assessed dye regurgitation in intravitreal ICG dye injections using HA-coated needles (HA needle group) and conventional needles (control group). Vitreous humor levels of anti-vascular endothelial growth factor (VEGF) were compared between groups one, three, and seven days after intravitreal bevacizumab (0.016 mL) injections. Expression levels of inflammatory cytokines in the aqueous humor and vitreous humor, including prostaglandin E2 (PGE2), interferon-γ, tumor necrosis factor-α, interleukin (IL)-1β, IL-4, IL-6, IL-17, and IL-8, were compared between HA needle, control, and normal (in which intravitreal injection was not performed) groups following 12 intravitreal injections over a period of one week. In the HA needle group, HA remained at the injection site and blocked the hole after intravitreal injection. Dye regurgitation occurred significantly less frequently in the HA needle group (16.7%) than the control group (55.6%) after intravitreal ICG dye injection. Meanwhile, vitreous anti-VEGF levels were markedly higher in the HA needle group than the control group one and three days after intravitreal bevacizumab injections. After 12 intravitreal injections, expression levels of aqueous and vitreous IL-8 significantly increased in the control group compared to the HA needle and normal groups. Conversely, there were no significant differences in the expression of the other seven cytokines among the three groups. Intravitreal injections using HA-coated self-sealing 30-gauge needles can block the outflow of vitreous humor and drugs through the needle passage.

Biomarkers of Neurodegeneration and Precision Therapy in Retinal Disease.

Vision-threatening retinal diseases affect millions of people worldwide, representing an important public health issue (high social cost) for both technologically advanced and new-industrialized countries. Overall RD group comprises the retinitis pigmentosa, the age-related macular degeneration (AMD), the diabetic retinopathy (DR), and idiopathic epiretinal membrane formation. Endocrine, metabolic, and even lifestyles risk factors have been reported for these age-linked conditions that represent a “public priority” also in this COVID-19 emergency. Chronic inflammation and neurodegeneration characterize the disease evolution, with a consistent vitreoretinal interface impairment. As the vitreous chamber is significantly involved, the latest diagnostic technologies of imaging (retina) and biomarker detection (vitreous) have provided a huge input at both medical and surgical levels. Complement activation and immune cell recruitment/infiltration as well as detrimental intra/extracellular deposits occur in association with a reactive gliosis. The cell/tissue aging route shows a specific signal path and biomolecular profile characterized by the increased expression of several glial-derived mediators, including angiogenic/angiostatic, neurogenic, and stress-related factors (oxidative stress metabolites, inflammation, and even amyloid formation). The possibility to access vitreous chamber by collecting vitreous reflux during intravitreal injection or obtaining vitreous biopsy during a vitrectomy represents a step forward for an individualized therapy. As drug response and protein signature appear unique in each single patient, therapies should be individualized. This review addresses the current knowledge about biomarkers and pharmacological targets in these vitreoretinal diseases. As vitreous fluids might reflect the early stages of retinal sufferance and/or late stages of neurodegeneration, the possibility to modulate intravitreal levels of growth factors, in combination to anti-VEGF therapy, would open to a personalized therapy of retinal diseases.

Effect of antiglaucoma agents on short-term intraocular pressure fluctuations after intravitreal bevacizumab injections.

To evaluate the effect of prophylactic pressure-lowering medications on intraocular pressure (IOP) spikes after intravitreal injections (IVIs) METHODS: In this randomized double-blind clinical trial, 74 eyes that were candidates for intravitreal anti-vascular endothelial growth factor (VEGF) injection (IVI) (0.05mL, 1.25mg of bevacizumab) were enrolled and sorted randomly into five groups, group 1: topical timolol 0.5% (n = 16); group 2: topical brimonidin (n = 15); group 3: oral acetazolamide 250mg (n = 14); group 4: intravenous mannitol (1.5 gr/kg) (n = 16); group 5: no intraocular pressure-lowering medication (n = 13). Medications were administered 30-60min prior to injection. None of the patients had history of glaucoma. Intraocular pressure was measured before (baseline), 5min after (T5), 10min after (T10), 15min after (T15) and 30min after (T30) IVI using Goldmann Tonometer. There was a statistically significant, but relatively weak negative correlation between the amount of vitreous reflux post-IVI intraocular pressure elevation (Spearman's rho = -0.315, p = 0.006). There was no difference of the amount of vitreous reflux (P = 0.196) between study groups. The baseline mean IOP for Groups 1, 2, 3,4 and 5 were 11.19 ± 3.7, 10.07 ± 2.19, 11 ± 2.98, 10.13 ± 3.48 and12.54 ± 2.60mmHg, respectively. (P = 0.214) There was no difference of peak IOP spike between groups at T5: 37 ± 19.7, 34.80 ± 15.76, 33.43 ± 18.29, 33.56 ± 16.88, 34.92 ± 9.99mmHg (P = 0.977). There was also no difference of IOP at T10, T15 and T30 between study groups: P = 0.979, P = 0.994 and P = 0.692, respectively. Although it is advisable to prevent IOP spikes, our study showed that use of prophylactic pressure-lowering medications with every mechanism of action has no effect in IOP spikes following intravitreal bevacizumab injections in non-glaucomatous eyes. Trial registrationThe study was registered with clinicaltrails.gov (ID# NCT02140450). Trial registration date: 05.09.2014.

Current intravitreal therapy and ocular hypertension: A review.

To determine the effect of commonly used intravitreal agents on immediate and long-term IOP elevations and their association, if any, with glaucoma. Literature searches in PubMed and the Cochrane databased in January 2020 yielded 407 individual articles. Of these, 87 were selected for review based on our inclusion criteria. Based on the evidence provided, 20 were assigned level I, 27 level II, and 22 level III. Eight articles were rejected because of poor quality, insufficient clarity, or irrelevance based on standardized protocols set out by the American Academy of Ophthalmology. The studies that reported on short-term IOP elevation (i.e., between 0 and 60 min) showed that an immediate increase in IOP is seen in all patients who receive anti-VEGF agents or triamcinolone acetonide when measured between 0 and 30 min of intravitreal injection and that the IOP elevation decreases over time. The data on long-term IOP elevation were mixed; Pretreatment with glaucoma medications, anterior chamber tap, vitreous reflux, longer intervals between injections, and longer axial lengths were associated with lower IOP elevations after injection of anti-VEGF agents, while the position of the implant vis-à-vis, the anterior chamber was important for steroid therapy. Data were mixed on the relationship between IOP increase and the type of intravitreal injection, number of intravitreal injections, preexisting glaucoma, and globe decompression before injection. There were no data on the onset or progression of glaucoma in the studies reviewed in this assessment. However, some studies demonstrated RNFL thinning in patients receiving chronic anti-VEGF therapy. Most, if not all, intravitreal agents cause ocular hypertension, both in the short term and long term. The functional consequences of these observations are not very clear.

Comparison between two intravitreal injection techniques with respect to fluid reflux, intraocular pressure, and therapeutic effect.

CONTEXT:Effect of fluid reflux on intraocular pressure (IOP) and therapeutic benefits.AIMS:The aim of this study is to compare two intravitreal injection techniques in terms of fluid reflux, short-term IOP changes, and therapeutic effect.SETTINGS AND DESIGN:A prospective, double-blinded, randomized interventional study.SUBJECTS AND METHODS:Sixty eyes were randomly allocated to two groups (direct intravitreal injection technique and oblique intravitreal injection technique). IOP was measured before and immediately after the injection of 0.1 ml comprising of bevacizumab (1.25 mg/0.05 ml) and dexamethasone (0.2 mg/0.05 ml) and then at 30 min after the injection. Occurrence and amount of vitreous reflux were recorded. Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were assessed preinjection and 6 weeks postinjection.RESULTS:IOP (mmHg ± standard deviation) increased significantly immediately after injection to 24.30 ± 3.02 (direct intravitreal injection) and 31.50 ± 3.49 (oblique intravitreal injection). These pressure rise differed significantly between both groups (mean difference: 7.2, P < 0.0001). Thirty minutes after injection, there was no significant difference in IOP increase between the groups. Occurrence and amount of fluid reflux were significantly higher with direct intravitreal injection. There was no significant difference in BCVA and CMT outcome between both groups.CONCLUSIONS:Direct intravitreal injection technique has lower rise in IOP and higher incidence of fluid reflux than the oblique intravitreal technique. Fluid reflux does not cause a therapeutic compromise in terms of BCVA or CMT changes, so the reflux fluid must be the vitreous not the drug. Thus, direct injection technique seems to be the preferred technique.

Can Vitreous Reflux Affect The Short-Term Treatment Response After Intravitreal Ranibizumab Injection?

ABSTRACT Purpose The aim of this study was to evaluate the effect of vitreous reflux (VR) on the short-term effect of intravitreal ranibizumab injection. Materials and Methods The study included 181 eyes of 81 age-related macular degeneration (AMD) and 100 diabetic macular edema (DME) patients. Treatment response was evaluated by measuring central macular thickness (CMT) as well as 1 mm and 3 mm central macular thicknesses (MT1 and MT3). Patients were grouped as; Group 1: no VR, Group 2: <3 mm VR, and Group 3: >3 mm VR according to conjunctival bleb diameters. The data were analyzed using variance, correlation and regression analyses. Results In AMD patients, reduction of CMT values following the treatment were 88.3 ± 110.6 µm in Group 1, 85.6 ± 158.7 µm in Group 2, and 93.1 ± 92.2 µm in Group 3. Likewise, in DME patients, it was 82.4 ± 88.4 µm, 72.9 ± 109.9 µm, and 73.7 ± 113.7 µm, respectively. Reduction of MT1 values after the treatment were 47.4 ± 72.6 µm, 36.0 ± 131.9 µm, and 36.7 ± 114.4 µm in AMD patients, and 33.3 ± 72.5 µm, 36.6 ± 90.2 µm, and 46.9 ± 83.4 µm in DME patients. In all comparisons among groups of VR, macular thickness (MT) change did not exhibit significant difference following an intravitreal ranibizumab treatment (p > .05). Conclusion We found that the increase in VR amount did not adversely affect the decrease in MT after intravitreal ranibizumab treatment in AMD and DME patients.

Vitreous Reflux Frequency and Intraocular Pressure After First-Time Intravitreal Aflibercept Injections: Comparison of 30- and 32-Gauge Needles.

PurposeTo compare the effects of 30-gauge versus 32-gauge needles on vitreous reflux (VR) frequency and intraocular pressure (IOP) following first-time intravitreal aflibercept injections.Materials and MethodsOverall, 116 patients (116 eyes) who received intravitreal injections using 30-gauge needles and 104 patients (104 eyes) who received the same injection using 32-gauge needles were reviewed. The medical records of 116 patients who each received an intravitreal injection using a 30-gauge needle (median age: 67.5 ± 13.9 years) and 104 patients who each received the same injection using a 32-gauge needle (median age: 66. 3 ± 10.6 years) from January 2015 to June 2019 were compared.ResultsNo significant difference in the frequency of VR was observed between patients injected using 30-gauge needles (38/116) and patients injected using 32-gauge needles (31/104, P = 0.64). There were no significant differences in the VR rates of patients with phakic and pseudophakic eyes between those injected using 30-gauge (P = 0.94) or 32-gauge needles (P = 0.77). Axial length did not significantly differ between patients with and without VR when injected using 30-gauge (P = 0.89) and with 32-gauge needles (P = 0.69). IOP immediately after injection was significantly higher in patients injected using 30-gauge needles than in patients injected using 32-gauge needles (P < 0.01).ConclusionVR frequency was not correlated with needle size, lens status, or axial length. Patients receiving injections using 30-gauge needles had higher IOP immediately after intravitreal injection.

Evaluation of vitreous reflux and intraocular pressure changes in repeated intravitreal injections

Evaluation of vitreous reflux and intraocular pressure changes in repeated intravitreal injections

Major factors affecting intraocular pressure spike after intravitreal ranibizumab injection: Vitreous reflux and its amount.

The aim of this study was to assess the effect of vitreous reflux and its amount on short-term intraocular pressure after intravitreal injection of ranibizumab. The study included 316 eyes of 276 patients. Intraocular pressures were measured before intravitreal injection (preIOP), immediately after intravitreal injection (postIOP0), and 30 min after intravitreal injection (postIOP30). The amount of vitreous reflux was evaluated by measuring conjunctival bleb diameter, and patients were grouped as; group 1: no vitreous reflux, group 2: less vitreous reflux, and group 3: more vitreous reflux. The data were analyzed using variance analysis, chi-square test, and regression analysis. PostIOP0 values were highest in group 1, followed by group 2 and group 3 (all p values < 0.001). PostIOP30 values were similar in group 1 and group 2 (p = 0.261), but were lower in group 3 than other two groups (p < 0.001, p = 0.001, respectively). Vitreous reflux was identified as the only factor affecting postinjection intraocular pressure changes (p < 0.001), and a negative correlation was found between the total number of intravitreal injection and vitreous reflux (p = 0.032). The major factor affecting short-term postinjection intraocular pressure elevation was vitreous reflux, and intraocular pressure levels increased as the amount of vitreous reflux decreased. Vitreous reflux and its amount decreased as the total number of intravitreal injection increased.

Intravitreal injection of low-dose gentamicin for the treatment of ERU-affected horses

Aim of the study was the retrospective evaluation regarding vision and recurrence in equine recurrent uveitis (ERU)-affected horses treated by intravitreal low-dose gentamicin injection in Tierklinik Alt Sammit during the years 2006-2013. The study included 50 equine patients (61 ERU-affected eyes) of different age and breed with different stages of ERU. The solution for the injection contained 4.0 mg sterile gentamicin per eye. The injection was performed according to the procedure described by Pinard et al. in 2005 under general anaesthesia in lateral recumbency of the patient and within a non-inflammatory period. The patients were monitored over a postoperative period of 2-96 months (mean 25.8 months, median 15 months). A total of 56 out of 61 treated eyes displayed no recurrence of ERU during the follow-up period. Recurrence of a single uveitic attack occurred in five eyes (8.2 %) within a period of 2 weeks to 28 months after surgery. Long-term stable vision was achieved in 43 out of 61 eyes (70.5 %). Postoperative blindness developed in 18 eyes, the majority hereof had already preoperatively displayed obvious pathologic ophthalmic findings with partly highly impaired vision. The main reason for a vision loss was the progression of a preoperatively existing cataract formation. Perioperative complications were limited to vitreous reflux into the subconjunctival space (two cases), subconjunctival haemorrhage in the area of the injection site (two cases), vitreous haemorrhage (one case) and two cases of immediate postoperative pain reaction associated with the intravitreal injection. The results of the therapy regarding the reduction of the recurrence rate and preservation of vision are comparable to those of vitrectomy. The complication rate is extremely low when using both the correct injection technique and amount of gentamicin solution. Therefore, the intravitreal injection of low-dose gentamicin is an inexpensive and uncomplicated alternative to vitrectomy.

The Effect of Anti-Vascular Endothelial Growth Factor Agents on Intraocular Pressure and Glaucoma: A Report by the American Academy of Ophthalmology

To assess the effect of intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents on immediate and long-term intraocular pressure (IOP) elevation and glaucoma. Literature searches of the PubMed and Cochrane databases, last conducted in April 2018, yielded 253 unique citations. Of these, 41 met the inclusion criteria and were rated according to the strength of evidence. Two articles were rated level I, 17 were rated level II, and 15 were rated level III; an additional 7 were excluded because of poor study design and lack of relevance to the topic under evaluation. The studies that reported on short-term IOP elevation (i.e., between 0 and 60 minutes) showed that an immediate increase in IOP is seen in all patients when measured between 0 and 30 minutes of intravitreal injection and that the IOP elevation decreases over time. The data on long-term IOP elevation were mixed; 7 studies reported that between 4% and 15% of patients developed sustained elevation of IOP at 9 to 24 months after injection, whereas 6 studies found no long-term change in IOP from 1 to 36 months after injection. Pretreatment with glaucoma medications, anterior chamber tap, vitreous reflux, longer intervals between injections, and longer axial lengths were associated with lower IOP elevations after injection. Data were mixed on the relationship between IOP increase and the type of intravitreal injection, number of intravitreal injections, preexisting glaucoma, and globe decompression before injection. There were no data on the onset or progression of glaucoma in the studies reviewed in this assessment. Intravitreal injection of anti-VEGF agents results in an immediate and transient increase in IOP. A long-term increase in IOP also may be seen, and further studies are needed to determine at-risk populations. Although there is some suggestion in the literature, there is currently insufficient data to determine the impact of intravitreal anti-VEGF injections on glaucoma progression. Although pretreatment with glaucoma medications, performing anterior chamber paracentesis, or increasing the interval between injections may reduce the impact of transient IOP elevation, the clinical significance and associated risks of these interventions are unknown.

A novel and less invasive technique to assess cytokine profile of vitreous in patients of diabetic macular oedema.

PurposeA pilot study to validate the collection of vitreous reflux (VR) after intravitreal injection using Schirmers tear strips was carried out. We assessed its efficiency for proteomics studies by estimating the differential expression of 27 cytokines using multiplexed bead array in diabetic macular oedema and proliferative diabetic retinopathy. To set, validate and assess the efficacy of Schirmer tear strips for collecting VR in patients undergoing intravitreal injections for diabetic macular oedema (DME).Patients and methodsVR samples were collected from 11 eyes of DME patients after intravitreal injections using Schirmer tear strips. Undiluted vitrectomy samples were obtained from six eyes of non-diabetic patients with idiopathic macular hole and seven eyes of diabetic patients with high-risk proliferative diabetic retinopathy (Hr-PDR), which were also subsampled on the Schirmer tear strips. Tear sampling was done in a subset of the DME patients. Total protein concentration between VR and vitrectomy samples was compared. Levels of the set of 27 cytokines in Schirmer tear strips samples were measured. Inter-group comparison for cytokines was done using Mann-Whitney U-test.ResultsSimilar protein concentration in VR samples and vitrectomy samples (P<0.05) was obtained. Tear protein contamination was not detected in VR samples. In comparison with no-DR patients, 25 and 20 of the measured 27 cytokines were significantly elevated (P<0.05) in the Hr-PDR and DME patients, respectively. As compared with no-DR patients, vascular endothelial growth factor was only moderately elevated in DME patients (P>0.05), but significantly elevated in Hr-PDR patients (P<0.05). Interleukin 1 receptor antagonist/interleukin 1b (IL1RA/IL1b) ratio was 13 times higher in DME patients as compared with Hr-PDR group.ConclusionWe demonstrated a simple, safe method of VR sampling. This technique provides a pure, albeit small, vitreous sample for proteomics. IL1RA/IL1b ratio was found to be 13-fold higher in the DME group as compared to the Hr-PDR.

Intraocular pressure after intravitreal injection of drugs

Corticosteroids, anti-vascular endothelial growth factor, antibiotics and antiviral were the main 4 classes of drugs for intravitreal injection. Depending on the class and volume of medication, age and gender of patients, ocular axial lengths or vitreous humour reflux, intraocular pressure (IOP) can be elevated transiently or persistently after intravitreal injection. Transient IOP elevation occurred in 2 weeks after intravitreal injection, and can be reduced to normal level for most patients. Only a small portion of such patients have very high IOP and need intervention measures such as anterior chamber puncture or lowering intraocular pressure by drugs. Long term IOP elevation is refers to persistent IOP increase after 2 weeks after intravitreal injection, and cause optic nerve irreversible damage and decline in the visual function of patients. Thus drug or surgical intervention need to be considered for those patients with high and long period of elevated IOP. Large-scale multicenter clinical trials need to be performed to evaluate the roles of the drug and patients factors for IOP of post- intravitreal injection, and to determine if it is necessary and how to use methods reducing IOP before intravitreal injection. Key words: Intravitreal injections/adverse effects; Intraocular pressure; Review