
The most important ophthalmology research updates, delivered directly to you.
The most important ophthalmology research updates, delivered directly to you.
In this week’s issue
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Ophthalmology
Efficacy of subcutaneous and intravenous tocilizumab in noninfectious uveitis
Tocilizumab can totally get it done, and it can do it subcutaneously. Tocilizumab (TCZ) is an immunosuppressive drug, specifically an IL-6 receptor antagonist, that is used off-label to treat noninfectious uveitis (NIU). Various immunosuppressants have been used in the treatment for noninfectious uveitis in the past with varying risk profiles. Biologics have become an increasingly effective alternative therapy, and they can be given subcutaneously (SQ) or intravenously (IV). This retrospective multicenter study aimed to assess the efficacy of SQ vs. IV Tocilizumab in 44 patients. 21 patients received only SQ treatment (162 mg every 1–2 weeks) while 21 patients received IV (4-8 mg/kg every 4 weeks). 2 patients were escalated from weekly SQ to IV TCZ. The primary outcome measure was treatment success based on anterior chamber cells, macular edema, ocular pain, amongst others. Overall, the study found that at 12 months of follow up, 20 out 27 (74%) patients seen at that time had successful inflammatory control, and there was no significant difference in efficacy between SQ and IV TCZ. Treatment success with TCZ was successful irrespective of indication for treatment or prior biologic failure. These findings suggest subcutaneous Tocilizumab can be an appropriate and effective treatment for non-infectious uveitis, even for treatment resistant patients.
JAMA Ophthalmology
Does empagliflozin help slow diabetic retinopathy in type 2 diabetes?
Empagliflozin: it’s not just for blood sugar, it might just keep your eyes from sugar-coating things. This cohort study explores the potential impact of empagliflozin, an SGLT2 inhibitor, on diabetic retinopathy (DR) progression in patients with type 2 diabetes (T2D). While the link between empagliflozin and the prevention of nonproliferative diabetic retinopathy (NPDR) remained unclear, empagliflozin was found to significantly reduce the risk of DR progression in patients with a history of NPDR compared to those treated with DPP4 inhibitors. The study included over 34,000 participants and used real-world data from commercial insurers and Medicare between 2014 and 2019. After an average follow-up of 8 months, there was no significant difference in the development of incident NPDR between the two groups, but those taking empagliflozin had a 22% lower risk of DR progression. These results highlight a potential benefit of empagliflozin in managing T2D patients with existing NPDR, offering clinical insights into its role as a therapy.
American Journal of Ophthalmology
Hemostasis with fibrin glue during surgery for proliferative diabetic retinopathy
The glue that holds us together! Patients with proliferative diabetic retinopathy (PDR) may experience retinal detachment and vitreous hemorrhage, often requiring surgical intervention. In diabetic patients, there is a high incidence of early post-operative vitreous cavity hemorrhage which requires subsequent treatment. This single masked pilot randomized control trial investigates the utility of intraoperative fibrin glue in preventing vitreous hemorrhage recurrence after primary vitreoretinal surgery in patients (n=20) with PDR. At 1-week and 4-weeks follow up, patients in the control group had significantly higher vitreous haze than their case group counterparts. Additionally, at 1 and 4 weeks, cases had more optically clear vitreous cavities (OR= 8.167, OR=33). Treatment for vitreous hemorrhage was required at 3 months post-op for 5 patients in the control group and 0 patients in the case group. The results of this study suggest that fibrin glue may be effective in preventing recurrence of vitreous hemorrhage after primary vitreoretinal surgery in patients with PDR. However, additional, larger-scale studies are required to assess long-term effects.
British Journal of Ophthalmology
Risk factors for neuropathic corneal pain after refractive surgery
Do we know enough to identify patients at risk of this feared complication? Refractive surgery is continuing to gain popularity because of excellent visual outcomes. However, neuropathic corneal pain (NCP) is a debilitating complication that can reduce the quality of life of young, otherwise healthy patients opting for this elective procedure. There are few studies addressing the epidemiology and risk factors for developing NCP. This prospective study included 100 patients undergoing bilateral SMILE or LASIK for myopia. Evaluation of ocular pain, ocular surface, in-vivo confocal microscopy and tear neuromediators was performed, and multivariate analyses were used to identify the risk factors associated with NCP. The incidence of NCP was 13.3% and 10.5% after SMILE and LASIK, respectively. In patients that underwent SMILE, preoperative refractive spherical equivalent was higher in the NCP group compared with the non-NCP group (p=0.02). In LASIK patients, the NCP group had poorer preoperative corneal nerve status compared with the non-NCP group [lower corneal nerve fiber length (p=0.02), lower nerve fractal dimension (p=0.003), higher nerve fiber width (p=0.04) and larger neuroma area (p=0.04)]. Postoperatively, the NCP group had significantly higher tear neuromediators such as tear nerve growth factor, calcitonin gene-related peptide, Frizzled class receptor 7 and nucleoside-diphosphate kinase. This study identifies risk factors for preoperative recognition of patients at risk for NCP as well as potential biomarkers and therapeutic targets for postoperative NCP.
Eye
Corneal vessels activity through the ‘Barcode sign’ of corneal OCT
Can we scan an OCT “barcode” to learn more about corneal vascularization? The use of anterior segment optical coherence tomography (AS-OCT) in corneal pathologies such as ectasia, keratitis, corneal dystrophies is widely known. Integrating AS-OCT in corneal vascularization (CVas) is not as well established. AS-OCT scans were obtained from 26 patients (26 eyes) with CVas of varying etiologies. Horizontal line scans from the AS-OCT, displaying vessel-induced back shadows (barcode sign with multiple vessels), were analyzed and compared with slit-lamp examination findings. Clinically, vessels were graded as active, partially regressed, and regressed. A total of 1092 AS-OCT scans from 26 eyes, representing all stages of corneal vascularization were analyzed. The back shadow (barcode sign with multiple vessels) was found in all 26 vessels studied (100%), casting a dense back shadow at the active stage. The back shadows were absent in 22 (84.62%) vessels during the regressed (healed) stage. The intensity of the back shadow decreased in 4 (15.38%) vessels at the regressing stage and did not demonstrate any active circulation and showed less distinctive back shadows. The brightness or lack of it, in the area of back shadow on the AS-OCT scan in the active stage (pre-treatment) and healed (post-treatment, partially regressed or ghost vessels) scans was statistically significantly different (P < 0.0001). This study highlights the value of AS-OCT in providing additional important information to assess and monitor vessel activity in patients with CVas. This can enable distinction between active and regressing/regressed vessels.
Ophthalmic Plastic and Reconstructive Surgery
The sweet truth behind droopy eyelids: Gestational diabetes and simple congenital ptosis
Gestational diabetes isn't just about sugar, it might also be stirring up a droopy dilemma for newborns. Simple congenital ptosis (SCP) is characterized by eyelid drooping during infancy and can lead to vision-threatening complications such as amblyopia. However, the exact etiology of SCP is unknown and likely multifactorial, and the underlying genetic and environmental factors remain unknown. This study aimed to identify obstetric risk factors for SCP and propose a possible pathophysiological mechanism. In this retrospective cohort study, 51 newborns diagnosed with SCP were compared to population data from a tertiary care center spanning 2002 to 2022. Newborns with SCP had significantly lower gestational ages (38.5 ± 2.6 vs 39.1 ± 1.7 weeks) and birth weights (2,998 ± 506g vs 3,255 ± 484g), and a higher incidence of maternal gestational diabetes (11.8% vs 5%) compared to the general population. Maternal age and C-section rates were similar between groups. This study pioneers a potential link between SCP and gestational diabetes, possibly mediated by disruptions in insulin-like growth factor 1 signaling. These findings highlight the importance of early ophthalmologic screening for at-risk newborns to improve outcomes related to SCP.
Luxturna Gene Therapy Phase III Trial - 2017
Welcome to the era of gene therapy. In this phase 3 clinical trial, 31 patients (age 3 and up) with biallelic RPE65 mutations and retinal dystrophy were randomized to either control (n=10) or intervention group (n=21) to receive bilateral subretinal injection of 1.5x1011 vg of AAV2-hRPE65v2 gene augmentation therapy. The primary outcome was ability to navigate low-to-medium light conditions, measured by multi-luminance mobility testing (MLMT) score.
Key Points:
This study demonstrated efficacy of voretigene neparvovec gene augmentation via improved functional vision in RPE65-mediated inherited retinal dystrophy. As the first study of its kind of a gene therapy for a genetic disease, this landmark trial additionally provided a foundation that has since been applicable to the treatment of other inherited vision disorders. For more on this interesting topic, listen to this podcast where Kathy High, one of the leaders of the RPE65 gene therapy phase 3 trial discusses this trial.
A 28-year-old male presented with sudden onset of blurred vision in both eyes after 2 days of hospitalization for severe epigastric pain and vomiting. He binged 1 L of alcohol 3 days back and had no previous history of binge drinking of significant past medical history. Visual acuity was counting fingers in both eyes. Fundus examination findings are shown below.
What is the most likely cause and mechanism of this patient’s intraocular hemorrhage?
A. Purtscher-like retinopathy; occlusion of arteriolar capillaries
B. Purtscher-like retinopathy; increased intraocular venous pressure
C. Terson retinopathy; increased intraocular venous pressure
D. Terson retinopathy; occlusion of arteriolar capillaries
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