Purpose: To compare the rates of clinically significant artifacts for two-dimensional peripapillary retinal nerve fiber layer (RNFL) thickness versus three-dimensional (3D) neuroretinal rim thickness using spectral-domain optical coherence tomography (SD-OCT). Methods: Only one eye per patient was used for analysis of 120 glaucoma patients and 114 normal patients. For RNFL scans and optic nerve scans, 15 artifact types were calculated per B-scan and per eye. Neuroretinal rim tissue was quantified by the minimum distance band (MDB). Global MDB neuroretinal rim thicknesses were calculated before and after manual deletion of B-scans with artifacts and subsequent automated interpolation. A clinically significant artifact was defined as one requiring manual correction or repeat scanning. Results: Among glaucomatous eyes, artifact rates per B-scan were significantly more common in RNFL scans (61.7%, 74 of 120) compared to B-scans in neuroretinal rim volume scans (20.9%, 1423 of 6820) (95% confidence interval [CI], 31.6-50.0; < 0.0001). For clinically significant artifact rates per eye, optic nerve scans had significantly fewer artifacts (15.8% of glaucomatous eyes, 13.2% of normal eyes) compared to RNFL scans (61.7% of glaucomatous eyes, 25.4% of normal eyes) (glaucoma group: 95% CI, 34.1-57.5, < 0.0001; normal group: 95% CI, 1.3-23.3, = 0.03). Conclusions: Compared to the most commonly used RNFL thickness scans, optic nerve volume scans less frequently require manual correction or repeat scanning to obtain accurate measurements. Translational Relevance: This paper illustrates the potential for 3D OCT algorithms to improve in vivo imaging in glaucoma.

Background: Visualization during scleral buckling is traditionally achieved via indirect ophthalmoscopy. Recent advances have utilized the surgical microscope and a 25 gauge cannula-based endoillumination system, also known as a Chandelier lighting system. This report details an improved approach using a guarded 25 or 27 gauge light pipe and the Ngenuity digital three dimensional platform. Methods: A standard Alcon light pipe is modified with a silicone guard to expose only 5 mm of the tip of the light pipe. The guard is created from the silicone that is already opened to secure the ends of the encircling band most often employed sleeve (e.g. 70, 270). This guarded light pipe is then inserted into the cannula as an alternative to a Chandelier lighting system. Results: This is a technical report of a surgical visualization technique using a three dimensional digital visualization platform with a modified handheld vitrectomy light pipe. Conclusion: The utilization of a guarded light pipe for visualization during primary scleral buckling is a promising, effective, and efficient technique. The three dimensional digital display allows for better educational impact and surgical communication with trainees and ancillary members of the surgical team.

Angiogenesis plays a key role in the pathology of diseases such as cancer, diabetic retinopathy, and age-related macular degeneration. Understanding the driving forces of endothelial cell migration and organization, as well as the time frame of these processes, can elucidate mechanisms of action of important pathological pathways. Herein, we have developed an organ-specific microfluidic platform recapitulating the in vivo angiogenic microenvironment by co-culturing mouse primary brain endothelial cells with brain pericytes in a three-dimensional (3D) collagen scaffold. As a proof of concept, we show that this model can be used for studying the angiogenic process and further comparing the angiogenic properties between two different common inbred mouse strains, C57BL/6J and 129S1/SvlmJ. We further show that the newly discovered angiogenesis-regulating gene Padi2 promotes angiogenesis through Dll4/Notch1 signaling by an on-chip mechanistic study. Analysis of the interplay between primary endothelial cells and pericytes in a 3D microfluidic environment assists in the elucidation of the angiogenic response.

There are multiple surgical approaches to the repair of rhegmatogenous retinal detachment (RRD). Here, we evaluated the outcomes of small-gauge pars plana vitrectomy (PPV), alone or in combination with scleral buckle (SB-PPV), for RRD repair using a standardized technique by 3 vitreoretinal surgeons: "extensive" removal of the vitreous with scleral depression and dynamic examination of the peripheral retina. One hundred eighty seven eyes of 180 consecutive patients treated for primary RRD by three vitreoretinal surgeons at a tertiary academic medical center from September 2015 to March 2018 were analyzed. Most RRDs occurred in males (134 [71.3%] eyes), affected the left eye (102 [54.3%]), and were phakic (119 [63.3%]). PPV alone was performed in 159 eyes (84.6%), with a combined SB-PPV used in the remaining 29 eyes (15.4%); focal endolaser was used in all (100%) cases. The single surgery anatomic success rate was 186 eyes (99.5%) at 3 months, and 187 (100%) at last follow up. Overall best-corrected visual acuity (BCVA) had significantly improved at 3 months ([Snellen 20/47] P<0.00005) and last follow up ([Snellen 20/31] P<0.00005), as compared to day of presentation ([Snellen 20/234]). Our findings suggest that "extensive" removal of the vitreous and dynamic peripheral examination with scleral depression may lead to high single surgery success in primary uncomplicated RRD repair.

PURPOSE: To report outcomes of secondary intraocular lens (IOL) implantation in the Infant Aphakia Treatment Study (IATS) SETTING:: Multicenter clinical practice DESIGN:: Secondary analysis of patients enrolled in a randomized clinical trial METHODS:: Details regarding all secondary IOL surgeries conducted in children enrolled in the IATS were compiled. We evaluated visual outcomes, refractive outcomes, and adverse events at age 10 ½ years. Comparisons were made to eyes that remained aphakic and to eyes randomized to primary IOL placement. RESULTS: 55/57 patients randomized to aphakia with contact lens correction were seen for the 10 ½ year study visit; 24/55 eyes (44%) had secondary IOL surgery. Median age at IOL surgery was 5.4 years (range 1.7 to 10.3 years). Mean absolute prediction error was 1.0 ± 0.7D. At age 10 ½ years, the median log MAR VA was 0.9 (range 0.2 to 1.7), similar to VA in the 31 eyes still aphakic (0.8, range 0.1 to 2.9); the number of eyes with stable or improved VA scores between the 4 ½ and 10 ½ year study visits was also similar (78% secondary IOL eyes, 84% aphakic eyes). For eyes undergoing IOL implantation after the 4.5 year study visit (n=22), the mean refraction at age 10 ½ years was -3.2 ±2.7D (range -9.9D to 1.1D), compared to -5.5 ±6.6 D (n=53, range -26.5 to 3.0D) in eyes with primary IOL (p=0.03). CONCLUSIONS: Delayed IOL implantation allows a more predictable refractive outcome at age 10 ½ years, though the range of refractive error is still large.

PURPOSE: To report the results of adjustable graded augmentation of superior rectus transposition, a novel modification of superior rectus transposition (SRT) designed to reduce postoperative vertical or torsional diplopia. METHODS: The medical records of patients who underwent adjustable graded augmentation of SRT with or without adjustable medial rectus recession (MRc) from February 2017 to December 2019 were reviewed retrospectively. A Mendez ring was used to monitor torsional change after transposition of the superior rectus muscle to the lateral rectus muscle and after sequential placement of 2 or 3 augmentation sutures by superior rectus-lateral rectus loop myopexy. If excessive mechanical intorsion was induced, the responsible augmentation suture was severed intraoperatively. If torsional or vertical diplopia was noted after recovery, the distal-most augmentation suture was cut. Exotropia was managed by severing the distal-most augmentation suture or by medial rectus adjustment. RESULTS: A total of 8 patients who underwent adjustable graded augmentation of SRT were included (6 using the 3-suture technique): 3 for esotropic Duane syndrome, 2 for abducens nerve palsy, 1 for Moebius syndrome, and 2 for combined trochlear and abducens nerve palsies. Of the 8 patients, 4 had prior strabismus surgery, and 1 patient had previously undergone treatment with botulinum toxin. Severing one augmentation suture in 3 cases resolved vertical (n = 2) or torsional (n = 1) diplopia and consecutive exotropia (n = 1), resulting in excellent alignment and reduction of torticollis to <4° in 7 cases. The technique proved insufficient in 1 patient, who had undergone 3 prior strabismus procedures. CONCLUSIONS: In this study cohort, adjustable graded augmentation of SRT effectively managed the risk of postoperative vertical or torsional diplopia.

PURPOSE: Infestation with demodex mites has been linked to the development of chalazion, meibomian gland dysfunction, and blepharitis. An effective treatment is the eyelid application of terpinen-4-ol (T4O), a tea tree oil component. However, T4O is also known to be toxic to nonocular epithelial cells. We hypothesize that T4O toxicity also extends to human meibomian gland epithelial cells (HMGECs). METHODS: Immortalized (I) HMGECs were cultured with varying concentrations (1.0%-0.001%) of T4O under proliferating or differentiating conditions up to 5 days. Experimental procedures included analyses of cell appearance, survival, P-Akt signaling, lysosome accumulation, and neutral lipid content. RESULTS: Our findings show that T4O causes a dose- and time-dependent decrease in the cell survival of IHMGECs. After 15 minutes of exposure to 1% T4O, IHMGECs exhibited rounding, atrophy, and poor adherence. Within 90 minutes of such treatment, almost all cells died. Reducing the T4O concentration to 0.1% also led to a marked decrease in P-Akt signaling and cell survival of IHMGECs. Decreasing the T4O amount to 0.01% caused a slight, but significant, reduction in the IHMGEC number after 5 days of culture and did not influence the ability of these cells to differentiate. CONCLUSIONS: T4O, even at levels 10-fold to 100-fold lower than demodicidal concentrations, is toxic to HMGECs in vitro.

Substance P (SP) is a tachykinin neuropeptide, implicated in the pathogenesis of various inflammatory conditions and a critical mediator in pain transmission. Recently, the role of SP was described in the pathogenesis of dry eye disease (DED) through its role in the maturation of antigen-presenting cells at the ocular surface after exposure to desiccating stress. However, the effect of SP on regulatory T cells (Tregs), which are functionally impaired in DED, remains unclear. This study examined the phenotypic and functional changes in Tregs in response to SP in DED. The in vitro cultures of normal Tregs in the presence of SP led to a significant reduction in both Treg frequencies and their suppressive function, which was prevented by the addition of an SP receptor (neurokinin-1 receptor) antagonist. Furthermore, in vivo treatment with the neurokinin-1 receptor antagonist in DED mice effectively restored Treg function, suppressed pathogenic T helper 17 response, and significantly ameliorated the disease. Our results show that a significant increase in SP levels promotes Treg dysfunction in DED, and blockade of SP effectively restores Treg function and suppresses DED severity.