Assessment of Zonular Integrity in Phakic Eyes Following Pars Plana Vitrectomy Using Ultrasound Biomicroscopy: A Prospective Paired Eye Comparative Study.

PURPOSE: To assess zonular integrity in phakic patients post vitrectomy using ultrasound biomicroscopy (UBM). DESIGN: Prospective, comparative, nonrandomized, double-masked, paired eye study. METHODS: We used ultrasound biomicroscopy (UBM) to evaluate phakic patients with a history of unilateral pars-plana vitrectomy. INCLUSION CRITERIA: (1) phakic patients with history of pars plana vitrectomy in one eye as the only procedure; (2) normal unoperated fellow eye; and (3) complete gas or air resolution from the vitreous cavity at the time of UBM assessment. EXCLUSION CRITERIA: (1) monocular patients; (2) history of intraoperative lenticular trauma; (3) the use of silicone oil tamponade; (4) history of trauma or pseudoexfoliation in either eye; (5) history of other ocular conditions that can affect the integrity of zonules, such as uveitis or ectopia lentis; (6) eyes with extreme myopia or long axial length (> -8.00 D or >30.0 mm); (7) history of intravitreal injection in either eye; (8) age <18 years. TECHNIQUE: A high-frequency (50 MHz) UBM device was used by a masked technician to obtain radial section images from zonular bundles at 8 different clock positions. Image quality was assessed in real time, captured, and saved. Two experienced masked observers (H.C. and C.B.) then assessed the quality of the images and graded the zonular findings. Only patients with adequate studies have been included. A unique grading system that was specifically devised for this study was used as the following: (0) clear, well-defined zonule(s); (1) uneven, disrupted zonules or stretched zonules; and (2) extensive loss of zonules. Each clock hour was graded according to this system and the total score was then calculated for each eye. In the primary outcome, 2 main groups were analyzed: vitrectomized eyes and healthy contralateral nonvitrectomized eyes. The mean total UBM score (TUS) from each group was compared and analyzed. RESULTS: Thirty-five patients were recruited into this study. Eleven patients were male and 24 were female. The mean age was 66.3 years. Thirty patients had vitrectomy for vitreomacular interface disorders (either macular hole or epiretinal membrane), 1 patient had vitreous hemorrhage and the remaining 4 patients had rhegmatogenous retinal detachments. With regard to tamponade agents, SF6 was used in 21 (60%) patients, air in 9 (26%) patients, and C3F8 in 5 (14%) patients. The mean TUS in the vitrectomized eyes was 2.28 (SD 1.83) vs 2.24 (SD 1.77) in the nonvitrectomized eyes (P = .9531). Overall, in the comparative analysis of mean scores based on 2 graders' assessments for each clock position in vitrectomized and nonvitrectomized eyes, there were no significant differences noted between the groups. CONCLUSION: This study found no evidence for a difference in the mean total UBM score in eyes following vitrectomy when compared to their contralateral healthy, nonvitrectomized eyes. This likely indicates that vitrectomy may not affect the integrity of zonules in phakic patients, at least for patients with vitreomacular interface disorders undergoing uncomplicated surgery.

Prognostic Features of Preoperative OCT in Retinal Detachments: A Systematic Review and Meta-analysis.

TOPIC: To evaluate the prognostic association between preoperative features seen on OCT imaging and postoperative visual acuity (VA) outcomes in rhegmatogenous retinal detachments (RRDs). CLINICAL RELEVANCE: Currently, there is limited literature on the prognostic value of preoperative RRD OCT features. METHODS: A literature search was conducted on Ovid MEDLINE, Ovid Embase, and Cochrane CENTRAL from inception to September 15, 2022. A meta-analysis was performed using a random-effects model. Quality of studies and evidence were assessed using the Joanna Briggs Institute tools and the Grading of Recommendations, Assessment, Development and Evaluation framework, respectively. RESULTS: A total of 1671 eyes of 1670 patients from 29 observational studies were included. Of these, 89% of eyes had a macula-off RRD at presentation. The mean average duration of detachment was 15 ± 10 days. Most eyes (62%) underwent pars plana vitrectomy. Six preoperative OCT features were analyzed: height of retinal detachment (HRD) at the fovea, central macular thickness (CMT), disruption of the ellipsoid zone (EZ) and/or external limiting membrane (ELM), intraretinal cystic cavities (ICCs), outer retinal corrugations (ORCs), and macular detachment. A greater HRD was weakly associated with postoperative VA (Pearson correlation r = 0.35; 95% confidence interval [CI], 0.20-0.48; P < 0.01), and there was no change in this association throughout the postoperative follow-up period. The CMT was not associated with postoperative VA. Eyes with disruption of the EZ and/or ELM had a postoperative VA worse by 0.35 logarithm of the minimum angle of resolution (logMAR) (95% CI, 0.15-0.54; P < 0.01) or 3 Snellen lines. Eyes with ICCs had a postoperative VA worse by 0.14 logMAR (95% CI, 0.01-0.26; P < 0.01) or 2 Snellen lines. Eyes with ORCs did not have a significantly different postoperative VA than eyes without ORCs. Eyes with macular detachment had a postoperative VA worse by 0.15 logMAR (95% CI, -0.31 to 0.00; P = 0.02) or 2 Snellen lines. Overall, the quality of studies ranged from moderate to good (73%-100%). All associations had a low quality of evidence, with CMT being of very low quality. CONCLUSION: Despite the low quality of evidence, a greater HRD, disruption of the EZ and/or ELM, presence of ICCs, and macular detachment were associated with a poor postoperative VA. We propose a standardized nomenclature for consistency and accuracy in reporting preoperative RRD OCT features for future studies. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Intraoperative Dexamethasone Intravitreal Implant (Ozurdex) in Vitrectomy Surgery for Epiretinal Membrane.

Objective: To study the effectiveness and safety of the intravitreal dexamethasone implant 0.7 mg (Ozurdex®) in vitrectomy surgery for epiretinal membrane.Methods: This is a prospective, multicenter, pilot study. Inclusion criteria included visually significant (<20/50) idiopathic epiretinal membrane. All patients underwent 23-gauge pars plana vitrectomy with membrane peeling and Ozurdex implant injection. The primary outcome measure was best corrected visual acuity (BCVA) change at 3 months. Secondary outcomes included BCVA at 6 months and changes in central retinal thickness (CRT). Intraocular (IOP) changes were monitored and cataract progression in phakic patients was documented.Results: 15 patients were enrolled in the study, 12 eyes of 12 patients were included in the analysis. Mean preoperative BCVA was 50.67 ETDRS letters and improved significantly to 63.67 (+12.91 letters, p = .008) at 3 months. Mean CRT improved from 548 to 409 microns (p = .002) at 3 months. The IOP showed mild elevation at months 1 and 2 and returned almost to baseline at month six. There were no complications related to the steroid implant injection procedure in an air-filled eye.Conclusions: Intra-operative injection of Ozurdex® at the conclusion of PPV can be done safely. The peak IOP and lowest CRT after 2 months strengthens the findings of prior studies demonstrating Ozurdex activity up to 3 months in vitrectomized eyes.

Aqueous Humor Cytokines and Long-Term Response to Anti-Vascular Endothelial Growth Factor Therapy in Diabetic Macular Edema.

PURPOSE: To determine the association of aqueous humor cytokine concentrations with long-term treatment response to anti-vascular endothelial growth factor (VEGF) agents in diabetic macular edema (DME). DESIGN: Retrospective case series. METHODS: Pooled data of aqueous humor cytokine concentrations collected at baseline and 2-month follow-up (2 injections) for treatment-naïve eyes with center-involving DME previously enrolled in a prospective study were reviewed. Subjects receiving intravitreal anti-VEGF injections outside of study protocol as per standard of care were classified into Responders versus Nonresponders based on qualitative assessment of optical coherence tomography for persistence of DME at longitudinal follow-up visits. RESULTS: Of the 41 eyes, 85% were classified as Responders with a significant decline in baseline central subfield thickness and macular volume (P values < .001), and 15% were identified as Nonresponders to anti-VEGF therapy over 51.4 ± 18.7 months of follow-up. No significant difference in baseline aqueous humor VEGF concentration was noted, while at the 2-month follow-up the Nonresponder group had a significantly higher VEGF concentration compared with the Responder group (451.5 ± 690.9 pg/mL vs 113.7 ± 211.4 pg/mL; P = .02). The Responder group also demonstrated a significant decline from baseline to 2-month follow-up in concentration of intercellular adhesion molecule-1 (P < .001), interleukin-10 (P = .041), monocyte chemotactic protein-1 (P = .046), placental growth factor (P = .027), and transforming growth factor-ß2 (P = .017). CONCLUSIONS: Aqueous humor cytokine concentrations serve as an early biomarker for long-term response to anti-VEGF therapy and may enable more effective treatment regimens that improve anatomical outcomes in eyes with DME.

Age-related macular degeneration: is polypoidal choroidal vasculopathy recognized and treated?

OBJECTIVE: To assess how polypoidal choroidal vasculopathy (PCV) is recognized and treated, and to assess whether treatment outcomes are different between Chinese and Caucasian Canadian patients with age-related macular degeneration (AMD). DESIGN: Retrospective chart review. PARTICIPANTS: 154 eyes from 135 Chinese patients and 2291 eyes from 1792 Caucasian patients who were newly diagnosed with either AMD or PCV and had more than 1 year of follow-up were included. METHODS: All newly diagnosed AMD patients presenting to the Retina Service of 3 Toronto University Hospitals, between March 25, 2008, to September 30, 2014, were reviewed. RESULTS: 10/154 eyes (6.5%) in Chinese Canadians and 16/2291 eyes (0.7%) in Caucasian Canadians were diagnosed as having PCV. Indocyanine green angiography (ICGA) was used to diagnose PCV in 20% of Chinese Canadians and 8.8% of Caucasian Canadians. Clinical practices with a larger percentage of Chinese patients were more likely to diagnose PCV in both Chinese (p = 0.004) and Caucasian patients (p = 0.03), were more likely to use photodynamic therapy (PDT) (p < 0.01), and had significantly greater central retinal thickness decrease (p < 0.001). CONCLUSION: Our study has shown that PCV is under-recognized in a Canadian population, and ICGA is underutilized. In clinical practices with a greater portion of Chinese patients, PCV is more often recognized and PDT is used more liberally.

Alterations in intraocular cytokine levels following intravitreal ranibizumab.

OBJECTIVE: Our previous work has shown that, after intravitreal bevacizumab (IVB) administration, decreases in the levels of vascular endothelial growth factor (VEGF)-A and placental growth factor (PlGF), along with increases in the levels of interleukin (IL)-8 and transforming growth factor (TGF)-ß2, can be observed. It is not yet known if similar changes occur after intravitreal ranibizumab (IVR). The purpose of this study was to examine intraocular cytokine changes after IVR. DESIGN: Prospective clinical study. PARTICIPANTS: Subjects with proliferative diabetic retinopathy requiring pars plana vitrectomy (PPV) were recruited. METHODS: Participants received IVR as pre-treatment before PPV. Aqueous humour levels of IL-8, VEGF-A, PlGF, and TGF-ß2 were measured at time of pre-treatment and PPV. Results were analyzed using univariate statistical models. RESULTS: A total of 14 participants were recruited. After IVR administration, we observed a decrease in the levels of VEGF-A and PlGF, and an increase in the levels of IL-8 and TGF-ß2. These results were statistically significant only for VEGF-A (p = 0.0001) and IL-8 (p = 0.0002). CONCLUSIONS: The changes in cytokine levels after IVR mirror the changes seen after IVB. Further studies are warranted in order to determine if there are any differences between IVB and IVR in this regard.

A randomized study comparing the efficacy of bevacizumab and ranibizumab as pre-treatment for pars plana vitrectomy in proliferative diabetic retinopathy.

BACKGROUND AND OBJECTIVE: To compare intravitreal bevacizumab versus ranibizumab as adjuvant treatment prior to pars plana vitrectomy (PPV) in proliferative diabetic retinopathy (PDR) with respect to parameters of surgical complexity. PATIENTS AND METHODS: Prospective, randomized, double-masked pilot study of patients requiring PPV for nonclearing vitreous hemorrhage or tractional retinal detachment (TRD) secondary to PDR. Patients were randomized to receive either intravitreal bevacizumab or ranibizumab at standard doses 1 week preoperatively. Measured parameters included total surgical time, presence of TRD, intraoperative bleeding, iatrogenic retinal breaks, and use of endolaser and endodiathermy or silicone oil. RESULTS: A total of 29 patients were recruited. For surgical parameters, there were no statistically significant differences between the groups in the univariate analyses. Multivariable analysis showed no statistically significant difference for total surgical time. CONCLUSION: This pilot study suggests that intravitreal bevacizumab and ranibizumab are equivalent as surgical adjuvants when used as pre-treatment in patients with PDR undergoing PPV.

Intravitreal ranibizumab for the treatment of fibrovascular pigment epithelial detachment in age-related macular degeneration.

OBJECTIVE: To determine the response of predominantly fibrovascular pigment epithelial detachments (PED)-type lesions (secondary to age-related macular degeneration [AMD]) to intravitreal ranibizumab. DESIGN: This was an open-label prospective study. PARTICIPANTS: Thirty-two patients with predominantly fibrovascular PED-type lesions secondary to AMD were included in this study. Three patients were excluded from the final analysis. METHODS: Patients received monthly intravitreal ranibizumab injections for 6 months (induction). At 6 months, patients not experiencing a visual improvement from baseline Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity or not showing a reduction in PED height (based on optical coherence tomography [OCT]) were deemed ranibizumab nonresponders and received no further injections but underwent re-evaluation at 12 months. Patients deemed responders continued with OCT-guided active treatment on an as-needed basis for an additional 6 months. RESULTS: Twenty-four patients (82.8%) were ranibizumab responders and 5 were (17.2%) nonresponders. For ranibizumab responders, mean ETDRS visual acuity improved by 7.2 ± 9.8 letters at 6 months (p = 0.002) and 6.3 ± 8.6 letters at 12 months (p = 0.002). Ranibizumab nonresponders experienced a decline in mean visual acuity of 8.2 ± 4.6 letters at 6 months (p = 0.02) and 18.2 ± 10.11 letters at 12 months (p = 0.02). At baseline, responders had a mean PED height of 345.8 ± 96.0 µm, which decreased to 111.6 ± 133.2 µm at 6 months (p < 0.001) and had a slight increase at 12 months to 144.8 ± 146.3 µm (p < 0.001). Two responders (8.3%) and 2 nonresponders (40%) developed retinal pigment epithelium tears while on treatment. CONCLUSIONS: Intravitreal ranibizumab appears to be a well-tolerated treatment option for patients with fibrovascular PED. Further large-scale, prospective studies may assist in delineating the best treatment protocol.

Antibiotic resistance of ocular surface flora with repeated use of a topical antibiotic after intravitreal injection.

IMPORTANCE: Treatment with intravitreal (IVT) injections has increased during the last several years as evidence has accumulated demonstrating the efficacy of anti-vascular endothelial growth factor agents in the treatment of neovascular age-related macular degeneration (AMD) and various retinal vascular diseases. Although IVT injections are generally safe, infectious endophthalmitis is a rare but devastating complication, and the risk of morbidity and vision loss from endophthalmitis is high. OBJECTIVE: To examine the change in antibiotic resistance of ocular surface flora with repeated prophylactic use of antibiotics after IVT injection for AMD. DESIGN AND SETTING: Prospective, nonrandomized cohort study in 2 tertiary academic hospitals. PARTICIPANTS: Patients 65 years and older with newly diagnosed AMD were recruited by 7 retinal specialists from July 1, 2010, through December 31, 2011. INTERVENTION: The study group received topical moxifloxacin hydrochloride for 3 days after each monthly IVT injection. MAIN OUTCOME MEASURE: Resistance to moxifloxacin and ceftazidime in cultured isolates at baseline and monthly for 3 months by change in minimal inhibitory concentration (MIC) of culture isolates was studied. RESULTS: The study group consisted of 84 patients, and the control group had 94 patients. In the study group, the baseline adjusted MIC increased (from 1.04 to 1.25 µg/mL; P = .01) as did the MIC for 50% of isolates (MIC50) (from 0.64 to 1.00 µg/mL) and the MIC for 90% of isolates (MIC90) (from 0.94 to 4.00 µg/mL). In both groups, the culture-positive rate did not change significantly when adjusted for baseline. No significant change was found in the MIC level, culture-positive rate, MIC50 level, and MIC90 level in the control group. Subgroup analysis found diabetes mellitus to be noncontributory to both the MIC and culture-positive rate. No endophthalmitis or adverse events were reported. CONCLUSIONS AND RELEVANCE: Repeated use of topical moxifloxacin after IVT injection significantly increases antibiotic resistance of ocular surface flora. We recommend that routine use of prophylactic antibiotics after IVT injection be discouraged. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01181713.

Effectiveness of intravitreal ranibizumab for the treatment of neovascular age-related macular degeneration in a Canadian retina practice: a retrospective review.

OBJECTIVE: To assess the effectiveness of intravitreal ranibizumab for neovascular age-related macular degeneration (AMD) in a tertiary care retina practice and compare these results with published efficacy data from randomized clinical trials. DESIGN: Nonrandomized, consecutive, single-centre, retrospective chart review analysis. PARTICIPANTS: Ninety-four patients (95 eyes) with neovascular AMD. METHODS: All treatment-naïve patients with neovascular AMD who received ranibizumab and for whom 1 year of follow-up was available were included in the analysis. The following information was gathered from each patient's chart: age, sex, ocular history, treated eye, duration of symptoms at presentation, subtype of choroidal neovascular membrane, Snellen visual acuity at each visit, number of injections, visits, and optical coherence tomography measurements. RESULTS: Subjects had a mean age of 81 (SD 7.11) years. The mean number of injections was 5.1 (SD 2.85) with a mean of 9.4 (SD 2.27) visits in the 12-month period. Overall, there was a gain of 2.88 (SD 24.6) letters in all eyes, and a loss of 2.5 (SD 23.1) letters in patients who met the visual acuity inclusion criteria for the clinical trials. Of the patients who met the inclusion criteria, 75% lost fewer than 15 letters and 11% gained more than 15 letters. CONCLUSIONS: Visual outcomes in our study patients compared poorly with the clinical trials. Possibilities for the disparity include gaps in the number and frequency of follow-up visits, patient or doctor assessment fatigue, or gaps in optical coherence tomography utilization and the number of injections administered.

Alterations in the intraocular cytokine milieu after intravitreal bevacizumab.

PURPOSE: Several complications after intravitreal bevacizumab (IVB) treatment have been described including tears of the retinal pigment epithelium and tractional retinal detachment. The etiology of these complications remains unclear. The purpose of this study was to characterize changes in the intraocular levels of inflammatory cytokines after IVB as a possible explanation for these complications. METHODS: Twenty-nine patients with proliferative diabetic retinopathy (PDR) undergoing pars plana vitrectomy (PPV) for vitreous hemorrhage (VH) with IVB pretreatment were prospectively enrolled. Aqueous humor samples were taken at the time of IVB pretreatment and approximately 1 week later at the time of PPV. Multiplex cytokine arrays were used to assay 20 different cytokines. Multivariate general linear regression was performed to determine differences in cytokine levels between the two study visits. Proportional hazards regression was performed to determine the relationship between cytokine levels at PPV and postoperative outcomes. RESULTS: After treatment with IVB, vascular endothelial growth factor (VEGF) concentrations in the aqueous humor decreased (P = 0.0003), whereas the concentrations of IL-8 and transforming growth factor (TGF)-beta(2) increased after IVB (P < 0.03). The level of IL-8 at the time of PPV was associated with the occurrence of recurrent VH after surgery (hazard ratio, 1.32; P = 0.02). CONCLUSIONS: Alterations in the intraocular inflammatory cytokine milieu occur after IVB injection, possibly as a compensatory mechanism in response to VEGF inhibition. The increased concentrations of inflammatory cytokines after IVB may be clinically significant and may be responsible for some of the complications after IVB.

Effect of prophylactic nonsteroidal antiinflammatory drugs on cystoid macular edema assessed using optical coherence tomography quantification of total macular volume after cataract surgery.

PURPOSE: To evaluate the efficacy of prophylactic administration of the topical nonsteroidal antiinflammatory drug (NSAID) ketorolac tromethamine 0.5% on acute (within 4 weeks of surgery) cystoid macular edema (CME) and total macular volume (TMV) in patients having phacoemulsification cataract surgery. SETTING: Department of Ophthalmology, Queen's University, Hotel Dieu Hospital, Kingston, Ontario, Canada. METHODS: This open-label nonmasked randomized (random number assignment) study comprised 106 eyes of 98 patients. Exclusion criteria included hypersensitivity to the NSAID drug class, aspirin/NSAID-induced asthma, and pregnancy in the third trimester. Ketorolac tromethamine 0.5% was administered starting 2 days before surgery and for 29 days after surgery for a total of 31 days. The outcome measure was macular swelling, which was quantified by the optical coherence tomography. RESULTS: At 1 month, there was a statistically significant difference in TMV between the control group (0.4420 mm3) and the ketorolac group (0.2392 mm3), with the ketorolac group having 45.8% less macular swelling (P = .009). Multiple linear regression with backward selection indicated a 44.3% (P = .013) and 46.1% (P = .030) reduction in macular swelling in the ketorolac group at 1 week and 1 month, respectively. CONCLUSION: Used prophylactically after cataract surgery, ketorolac 0.5% was efficacious in decreasing postoperative macular edema.

Retinal toxicity of intravitreal ganciclovir in rabbit eyes following vitrectomy and insertion of silicone oil.

BACKGROUND: Although intravitreal ganciclovir dosages up to 500 microg have been demonstrated to be safe in some studies, other studies have shown toxic retinal effects in rabbit eyes without silicone oil at lower dosages. In current clinical practice, the same dosage of intravitreal antiviral agent is given regardless of whether there has been retinal detachment repair with silicone oil. We performed a study to investigate, in rabbit eyes following vitrectomy and silicone oil insertion, the retinal toxicity of serial intravitreal injections of ganciclovir, using dosages previously found not to produce significant toxic effects in nonvitrectomized eyes. METHODS: Twenty-eight eyes of 14 New Zealand pigmented rabbits underwent pars plana vitrectomy and silicone oil insertion. One eye of each animal received an intravitreal ganciclovir injection twice weekly for 2 weeks. The other eye received 0.1 mL of normal saline as a control. Three dosages of ganciclovir (50, 100 or 200 microg/0.1 mL) were used in three groups of three to six animals. Scotopic electroretinography and histologic examination were performed 2 weeks postoperatively. RESULTS: No differences in scotopic b-wave threshold (p = 0.23, 0.78 and 0.50 for ganciclovir dosages of 50, 100 and 200 microg/0.1 mL respectively, Mann-Whitney U test) or in light microscopy findings were noted between the treatment and control eyes at any dosage of ganciclovir. Surgical complications were observed in eight eyes; the data for these eyes were not used for analysis. INTERPRETATION: Ganciclovir dosages of up to 200 microg/0.1 mL appear to be safe for serial intravitreal injection in rabbit eyes following vitrectomy and silicone oil insertion.