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.
Purpose: Because preterm birth and retinopathy of prematurity (ROP) are associated with poor visual acuity (VA) and altered foveal development, we evaluated relationships among the central retinal photoreceptors, postreceptor retinal neurons, overlying fovea, and VA in ROP. Methods: We obtained optical coherence tomograms (OCTs) in preterm born subjects with no history of ROP (none; n = 61), ROP that resolved spontaneously without treatment (mild; n = 51), and ROP that required treatment by laser ablation of the avascular peripheral retina (severe; n = 22), as well as in term born control subjects (term; n = 111). We obtained foveal shape descriptors, measured central retinal layer thicknesses, and demarcated the anatomic parafovea using automated routines. In subsets of these subjects, we obtained OCTs eccentrically through the pupil (n = 46) to reveal the fiber layer of Henle (FLH) and obtained adaptive optics scanning light ophthalmograms (AO-SLOs) of the parafoveal cones (n = 34) and measured their spacing and distribution. Results: Both VA and foveal depth decreased with increasing ROP severity (term, none, mild, severe). In severe subjects, foveae were broader than normal and the parafovea was significantly enlarged compared to every other group. The FLH was thinner than normal in mild (but not severe) subjects. VA was associated with foveal depth more than group. Density of parafoveal cones did not differ significantly among groups. Conclusions: Foveal structure is associated with loss of VA in ROP. The preserved FLH in severe (relative to mild) eyes suggests treatment may help cone axon development. The significantly larger parafovea and increased outer nuclear layer (ONL) thickness in ROP hint that some developmental process affecting the photoreceptors is not arrested in ROP but rather is supranormal.
Cyclodestruction aims to reduce aqueous humor production through the coagulation or destruction of the ciliary body and has been an important treatment choice for glaucoma since the 1930s. The purpose of the current review is to highlight the evidence regarding the safety and efficacy of various cyclodestructive modalities, emphasizing peer-reviewed articles from the last 20 years and the most common variants of these procedures. The review focuses primarily on the two most common variants of transscleral cyclophotocoagulation (TS-CPC), continuous-wave diode cyclophotocoagulation (CW-TSCPC) and MicroPulse diode cyclophotocoagulation (MP-TSCPC) as well as endoscopic cyclophotocoagulation (ECP) and high-intensity focused ultrasound cyclodestruction (HIFU). We believe that the role of cyclodestruction in glaucoma treatment will only continue to expand given the advances in the field, particular with regards to targeted ciliary body destruction and improvement in the safety profile.
PURPOSE: To evaluate the association of retinal nonperfusion and diabetic retinopathy (DR) severity with location of vascular caliber measurement using ultrawide field (UWF) imaging. DESIGN: Retrospective image review SUBJECTS: Adult subjects with diabetes mellitus. METHODS: All images from subjects with same day UWF fluorescein angiography (FA) and color imaging (CI) were evaluated. DR severity and predominantly peripheral lesions (PPL) were graded from UWF-CI. Nonperfusion was quantified using UWF-FA in defined retinal regions [posterior pole (PP), mid-periphery (MP), far-periphery (FP)]. Retinal vessel calibers were measured at an inner and outer zone centered on the optic disc. MAIN OUTCOME MEASURES: Nonperfusion index (NPI) in the PP, MP and FP. Mean arteriole and venule diameter in the inner and outer zones. RESULTS: 285 eyes of 193 patients [(24.9% mild nonproliferative DR (NPDR), 22.8% moderate, 37.5% severe and 14.7% proliferative DR (PDR)] were reviewed. There were no significant associations between inner zone arteriolar diameter and retinal NPI overall or in any retinal region. In the outer zone, eyes with thinnest arteriolar calibers (Q1) were associated with a 1.7-2.4-fold increase in nonperfusion across all retinal regions compared to the remaining eyes [P=0.002 (PP) to 0.048 (FP)]. In the outer zone, the percentage of eyes in the thinnest quartile of retinal arteriolar diameter increased with worsening DR severity (10% in mild NPDR and 31% in PDR, p=0.007). This association was not observed when measured within the inner zone (p=0.129). All venular caliber associations were not statistically significant when corrected for potentially confounding factors. Thinner outer zone retinal arteriolar caliber (Q1) was more common in eyes with PPL compared to eyes without PPL (34.1% vs 20.8%, p=0.017) as were thicker outer venular calibers (Q4) (33% vs 21.3%, p=0.036). Presence of PPL was associated with thinner outer zone arteriolar caliber (109.7±26.5 vs 123.0±29.5, p=0.001). CONCLUSIONS: The association of vascular caliber with nonperfusion and DR severity differs based upon the retinal location at which vascular caliber is measured. Peripheral arterial narrowing is associated with increasing nonperfusion, worsening DR severity and presence of PPL. In contrast, inner zone retinal arteriolar caliber is not associated with these findings.
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.
Virtual visits (VVs) are necessitated due to the public health crisis and social distancing mandates due to COVID-19. However, these have been rare in ophthalmology. Over 3.5 years of conducting >350 ophthalmological VVs, our group has gained numerous insights into best practices. This communication shares these experiences with the medical community to support patient care during this difficult time and beyond. We highlight that mastering the technological platform of choice, optimizing lighting, camera positioning, and "eye contact," being thoughtful and creative with the virtual eye examination, and ensuring good documenting and billing will make a successful and efficient VV. Moreover, we think these ideas will stimulate further VV creativity and expertise to be developed in ophthalmology and across medicine. This approach, holds promise for increasing its adoption after the crisis has passed.
PURPOSE: In humans, loss-of-function mutations in the gene encoding Chordin-like 1 (CHRDL1) cause X-linked megalocornea (MGC1), characterized by bilateral corneal enlargement, decreased corneal thickness, and increased anterior chamber depth (ACD). We sought to determine whether Chrdl1 knockout (KO) mice would recapitulate the ocular findings found in patients with MGC1. METHODS: We generated mice with a Chrdl1 KO allele and confirmed that male Chrdl1 hemizygous KO mice do not express Chrdl1 mRNA. We examined the eyes of male mice that were hemizygous for either the wild-type (WT) or KO allele and measured corneal diameter, corneal area, corneal thickness, endothelial cell density, ACD, tear volume, and intraocular pressure. We also harvested retinas and counted retinal ganglion cell numbers. Eye segregation pattern in the dorsal lateral geniculate nucleus were also compared between male Chrdl1 KO and WT mice. RESULTS: Male Chrdl1 KO mice do not have larger cornea diameters than WT mice. KO mice have significantly thicker central corneas (116.5 ± 3.9 vs. 100.9 ± 4.2 μm, P = 0.013) and smaller ACD (325.7 ± 5.7 vs. 405.6 ± 6.3 μm, P < 0.001) than WT mice, which is the converse of what occurs in patients who lack CHRDL1. Retinal-thalamic projections and other ocular measurements did not significantly differ between KO and WT mice. CONCLUSIONS: Male Chrdl1 KO mice do not have the same anterior chamber abnormalities seen in humans with CHRDL1 mutations. Therefore, Chrdl1 KO mice do not recapitulate the human MGC1 phenotype. Nevertheless, Chrdl1 plays a role during mouse ocular development because corneas in KO mice differ from those in WT mice.
PURPOSE: Fatty infiltration of the extraocular muscles has been described radiographically in patients with thyroid eye disease (TED), yet it has not been studied on a large scale nor quantified. Our purpose was to define and characterize this entity in patients with TED. METHODS: An IRB-approved cross-sectional retrospective review of medical records identified patients with a clinical diagnosis of TED and at least one CT of the orbits. A 2:1 age and sex-matched control population consisted of patients without a history nor radiographic evidence of orbital disease or systemic thyroid abnormality. The presence of fatty infiltration in each extraocular rectus muscle was defined using Hounsfield units (HU). Laterality, muscles involved, and pattern of fatty infiltration were also evaluated. Student's t-tests, Chi-square, and Fisher's exact tests were used to compare TED and control groups. RESULTS: The study population consisted of 252 patients with TED and 504 age and sex-matched controls. Fatty infiltration was significantly more prevalent in TED patients (36/252, 14.3%) compared to controls (11/504, 2.2%) ( < .001). The mean density of fat infiltration was significantly lower in TED patients (-40.4 HU) than controls (-34.8 HU) ( = .048). In TED patients, the frequency of muscle involvement was inferior rectus (61.8%), lateral rectus (19.7%), superior rectus (11.8%) and medial rectus (6.6%), which was not significantly different than controls ( > .05). Most muscles (88.2%) in the TED group exhibited a heterogeneous pattern of infiltration, which did not differ from controls ( = .34). CONCLUSIONS: This study characterizes fatty infiltration of the extraocular muscles in patients with TED.
PURPOSE: The origin of blood in glaucoma-related disc hemorrhages (DH) remains unknown. A prior clinic-based study of primary open-angle glaucoma (POAG)-related DH showed that they had grayscale pixel intensities more similar to blood from retinal macroaneurysms and adjacent retinal arterioles than to blood from retinal vein occlusions or adjacent retinal venules, suggesting an arterial source. Here we assessed the densitometric profile of DH from fundus photographs in the Ocular Hypertension Treatment Study (OHTS). DESIGN: Retrospective cross-sectional study of prospectively collected images. METHODS: Stereo disc photographs of 161 DH events from 83 OHTS participants (mean age [standard deviation (SD)]: 65.6 [9.2] years; 46.6% female; 13.0% black race) were imported into ImageJ to measure densitometry differences (adjacent arterioles minus DH [ΔA] or venules minus DH [ΔV]). Their size as percentage of disc area, ratio of length to midpoint width, and location relative to the disc margin were also analyzed. We performed t tests to compare ΔA and ΔV, analysis of variance to compare ΔA and ΔV across DH recurrent events, and multivariable linear regression to identify determinants of ΔA and ΔV. RESULTS: Mean (SD) ΔA and ΔV were -2.2 (8.7) and -11.4 (9.7) pixel intensity units, respectively (P < .001). ΔA and ΔV each did not differ significantly across recurrence of DH (P ≥ .92) or between DH events with and without POAG (P ≥ .26). CONCLUSIONS: OHTS DH had densitometric measurements more similar in magnitude to adjacent arterioles than venules, supporting an arterial origin for DH. Vascular dysregulation may contribute to disc hemorrhage formation in ocular hypertension.
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.
Autoimmune retinopathy (AIR) refers to a group of rare autoimmune retinal degenerative diseases presumably caused by cross-reactivity of serum autoantibodies against retinal antigens. The pathogenesis of AIR remains largely presumptive and there are a significant number of antiretinal antibodies that have been detected in association with AIR. The diagnosis of AIR is largely based on the demonstration of antiretinal antibodies in the serum along with suggestive clinical features and ancillary investigations. A high index of suspicion along with early diagnosis and treatment may play a critical role to lower the risk of irreversible immunological damage to the retinal cells in these patients. A multi-disciplinary approach for complete management and evaluation is helpful in such conditions. Various therapeutic options have been described for the treatment of AIR, though there is no consensus on standard treatment protocol.
PURPOSE: To evaluate the outcomes of inferior oblique (IO) weakening surgery, whether recession or myectomy, and to assess the dose-response relationship and correlation with angle of preoperative hypertropia. METHODS: The medical records of all patients with vertical deviation in primary gaze who underwent unilateral IO-weakening surgery, either recession or myectomy, at Boston Children's Hospital over an 8-year period with a minimum postoperative follow-up of 1 month were reviewed retrospectively. Outcome measures were effect of IO weakening surgery on vertical deviation in primary gaze and its correlation with the preoperative angle of hyperdeviation. Secondary outcomes included resolution of abnormal head posture, reduction of ocular torsion, and postoperative under- and overcorrection RESULTS: A total of 94 patients were identified (mean age at surgery, 29.3 ± 19.8 years; range, 1-69). The mean postoperative follow-up period was 17.2 ± 15 months. IO recession was performed in 30 patients; IO myectomy, in 64. Surgical success in primary position was achieved in 72 patients (77%), with resolution of anomalous preoperative head posture in 93%. The mean effect on alignment in primary position was 11.3 ± 6.8. The response to IO-weakening surgery was strongly correlated with the preoperative hyperdeviation for both recession (R = 0.53) and myectomy (R = 0.87). CONCLUSIONS: As with other types of strabismus surgery, IO weakening has a "self-grading" contribution, in which the surgical effect strongly correlates with the magnitude of preoperative deviation. A large range of vertical misalignment can be corrected with the same surgical approach.
A 43-year-old woman was referred with a 10 month history of persistent pain in the left orbit. Two years prior, she experienced similar pain in the right orbit. Magnetic resonance imaging (MRI) at the time revealed an enlarged right medial rectus muscle. She was diagnosed with idiopathic orbital myositis and was successfully treated with oral corticosteroids. A year later, she developed symptoms in the left orbit with similar imaging findings. For ten months, she remained on high dose corticosteroids for presumed left medial rectus myositis before presenting to our service. Computed tomography (CT) imaging after corticosteroid taper revealed enlarged left medial rectus and left lateral rectus muscles. Orbital biopsy established a diagnosis of granulomatosis with polyangiitis (GPA), for which she was successfully treated with rituximab. This case underscores the importance of not only proceeding with biopsy in atypical cases of orbital myositis but to also taper steroids prior to biopsy.
PURPOSE: Assess follow-up treatment and clinical outcomes at 5 years in eyes initially treated with anti-VEGF therapy for center-involved diabetic macular edema (CI-DME) in a 2-year randomized clinical trial. DESIGN: Multicenter cohort study. PARTICIPANTS: Participants with diabetic macular edema (DME) and visual acuity (VA) 20/32 to 20/320 enrolled in DRCR.net Protocol T with visits 5 years after randomization (3 years after Protocol T completion). METHODS: Participants were assigned randomly to aflibercept, bevacizumab, or ranibizumab with protocol-defined follow-up and re-treatment for 2 years. Thereafter, participants were managed at clinician discretion and recalled for a 5-year visit. MAIN OUTCOME MEASURES: Anti-vascular endothelial growth factor (VEGF) treatment, VA letter score, and central subfield thickness (CST). RESULTS: Sixty-eight percent (317/463) of eligible participants completed the 5-year visit. Between years 2 and 5, 68% (217/317) of study eyes received at least 1 anti-VEGF treatment (median, 4; interquartile range [IQR], 0-12). At 5 years, mean VA improved from baseline by 7.4 letters (95% confidence interval [CI], 5.9-9.0) but decreased by 4.7 letters (95% CI, 3.3-6.0) between 2 and 5 years. When baseline VA was 20/50 to 20/320, mean 5-year VA was 11.9 letters (95% CI, 9.3-14.5) better than baseline but 4.8 letters (95% CI, 2.5-7.0) worse than 2 years. When baseline VA was 20/32 to 20/40, mean 5-year VA was 3.2 letters (95% CI, 1.4-5.0) better than baseline but 4.6 letters (95% CI, 3.1-6.1) worse than 2 years. Mean CST decreased from baseline to 5 years by 154 μm (95% CI, 142-166) and was stable between 2 and 5 years (-1 μm; 95% CI, -12 to 9). CONCLUSIONS: Among the two-thirds of eligible Protocol T participants who completed a 5-year visit, mean VA improved from baseline to 5 years without protocol-defined treatment after follow-up ended at 2 years. Although mean retinal thickness was similar at 2 and 5 years, mean VA worsened during this period. Additional investigation into strategies to improve long-term outcomes in eyes with DME seems warranted to determine if VA can be better maintained with different management approaches.
Purpose: To report a patient with post-operative gas migration into the optic nerve and lateral ventricles after retinal detachment repair. Observations: A 78-year-old pseudophakic man developed a temporal visual field cut in his non-operative, right eye 3 weeks after repair of a recurrent, shallow, macula-involving retinal detachment with perfluoropropane intraocular gas in the left eye. Visual acuity in the right eye measured 20/40, and static perimetry demonstrated temporal visual field loss that respected the vertical midline. Dilated fundus examination of the right eye was unrevealing for any retinal cause, raising suspicion for an intracranial etiology. An urgent CT scan of the brain demonstrated gas in all segments of the left optic nerve and lateral ventricles, consistent with intracranial gas migration along the optic nerve. Given the absence of systemic neurologic symptoms, cautious observation was advised on consultation with neuroradiology and neurosurgery, and follow-up CT scan 1 week later showed resolution of the intracranial gas. By 10-weeks post-operatively, vision returned to 20/20 in the right eye with persistent temporal field loss, and the left eye was hand motions (20/70 pre-operatively) with evidence of optic nerve atrophy and severe cupping. Conclusions: Intracranial gas migration is a rare complication of retinaldetachment repair with intraocular gas and may occur in the setting of structural defects of the optic nerve and high post-operative intraocular pressure. Clinicians should be alert to this rare but serious complication, which can cause neurologic symptoms and result in vision loss in both the operative and non-operative eyes.