Long-term outcomes of modified glued versus flanged intrascleral haptic fixation techniques for secondary intraocular lenses.

PURPOSE: To report the long-term refractive outcomes and complications of two scleral fixation techniques for secondary intraocular lenses (IOL). METHODS: Consecutive patients who underwent secondary IOL insertion at a tertiary care academic hospital using either modified glued ("glued") or flanged intrascleral haptic fixation (FISHF) techniques with over 12 months of follow-up were retrospectively reviewed. Pre- and postoperative corrected distance visual acuity (CDVA), postoperative complications, and refractive surprises were reported. RESULTS: Thirty-eight patients underwent "glued" fixation and 22 underwent FISHF, with mean follow-up times of 3.1 ± 0.5 and 2.0 ± 1.2 years, respectively. Aphakia secondary to trauma was the main surgical indication. MA50BM or MA60AC IOLs (Alcon Laboratories Inc., Fort Worth, TX) were implanted in 92% of "glued" patients, while CT Lucia 602 IOLs (Carl Zeiss Meditec Inc., Dublin, CA) were used in 96% of FISHF patients. Postoperative spherical equivalent significantly improved compared to preoperative values (p < 0.001). No significant difference in CDVA was seen between the two techniques. FISHF resulted in mean hyperopic surprises of + 0.81D and + 0.69D using the Holladay 2 and Barrett Universal II formulae, respectively, which was significantly greater than the "glued" patients. A higher rate of IOL dislocation was seen in the "glued" cohort (13%) compared to FISHF (0%). CONCLUSIONS: Retrospective long-term outcomes of patients with complex ocular comorbidities undergoing a modified "glued" technique demonstrated a higher rate of IOL dislocation but more predictable refractive outcomes compared to the FISHF technique. The FISHF technique resulted in a significant hyperopic shift using fourth-generation IOL calculators.

Outcomes of sutureless secondary intraocular lens fixation with haptic flanging in a cohort of surgically complex eyes.

PURPOSE: To describe clinical outcomes of secondary intraocular lens (IOL) implantation using sutureless trans-scleral techniques in surgically complex eyes. METHODS: Retrospective surgical case series of 45 eyes that underwent secondary IOL implantation using a sutureless haptic flange technique. Demographic data of age, sex, primary diagnosis, best-corrected visual acuity (BCVA), refractive error, intraocular pressure, full ophthalmic exam findings, surgical approach, and any intraoperative complications were noted. RESULTS: The most common indication for secondary IOL implantation was aphakia, most commonly after ocular trauma. The primary outcome measures were pre-operative and post-operative BCVA, which revealed recovery of pre-operative vision levels by post-operative week 1 and improved vision by post-operative month 1 (p = 0.03). Secondary outcome measures of target refraction pre-operatively and post-operatively revealed significant reduction in post-operative spherical equivalent to achieve BCVA (p < 0.001). Targeting of the secondary IOLs using Barrett Universal II, Holladay 1, Holladay 2, and SRK/T all exhibited a hyperopic shift post-operatively in post-traumatic aphakic eyes and a myopic shift in the post complicated cataract extraction eyes. No intraoperative adverse events were noted. The most common post-operative complication was transient IOP elevation, with most patients completing 6 months of follow-up. CONCLUSION: There is rapid visual rehabilitation and reduction of spherical equivalent correction to attain BCVA in eyes with a history of ocular trauma that undergo secondary IOL implantation using a trans-scleral flange technique. Moreover, this study highlights that a specific IOL power formula can be more predictive of the desired refractive outcome depending on the indication for secondary IOL implantation.

Effect of prior glaucoma surgery on intraocular pressure immediately after anti-vascular endothelial growth factor injection.

BACKGROUND: To characterize how prior incisional glaucoma surgery affects the intraocular pressure (IOP) elevation immediately following intravitreal anti-VEGF injections (IVI). METHODS: Single institution, experimental study. Patients with a history of incisional glaucoma surgery who were receiving anti-VEGF injections were recruited as well as control eyes. Pre- and post-injection IOP measurements were compared as well as time to recovery to within 5 and 10 mmHg of baseline IOP. RESULTS: Ten eyes with a history of glaucoma surgery and 29 control eyes receiving anti-VEGF injections were included. The most common indication for intravitreal anti-VEGF injection was proliferative diabetic retinopathy in both surgical and control eyes (50% vs 45%, p = 1.00). Post-injection IOP was significantly decreased compared to baseline IOP after anti-VEGF injection in surgical versus control eyes (26.5 ± 8.9 mmHg vs 44.2 ± 8.5 mmHg, respectively, p < 0.001). The mean change in IOP following intravitreal anti-VEGF injection was lower in surgical eyes (10.7 ± 6.6 mmHg vs 28.6 ± 8.3 mmHg, p < 0.001). The mean time for the IOP to return to within 10 mmHg of pre-injection IOP was less in surgical eyes (5.2 ± 4.1 min vs 13.3 ± 7.6 min, p = 0.002). CONCLUSIONS: Eyes with prior incisional glaucoma surgery demonstrated a significantly lower post-injection IOP elevation and a faster recovery to within 10 mmHg of their pre-injection IOP. Incisional glaucoma surgery may be considered for patients where the attenuation of post-injection IOP elevation is needed and other less invasive measures have failed.

Retinal and choroidal vascular features in patients with retinitis pigmentosa imaged by OCT based microangiography.

PURPOSE: To image vascular features of retinitis pigmentosa (RP) using optical coherence tomography angiography (OCTA). METHODS: Patients with RP were imaged by spectral domain optical coherence tomography based angiography (OCTA). The optical microangiography (OMAG) algorithm was applied to scanned datasets to generate 3D OCTA retinal angiograms, i.e., OMAG angiograms. Motion tracking was used to minimize artifacts due to eye movement, and large field of view OMAG angiograms were achieved through a montage scanning protocol. For better visualization, depth volumes were segmented to separate the superficial retinal layers from deep outer retinal layers. The choriocapillaris and other choroidal layers were also segmented. To investigate the changes in retinal architecture, the inner segment/outer segment (IS/OS) junction to RPE layer was segmented to generate en face structural images through averaging intensity projection. Color fundus images and/or Goldmann visual fields were available for comparison of the findings to OMAG images. RESULTS: A total of 25 eyes (13 patients, seven women and six men) diagnosed with RP at various stages were enrolled in this study from October 2014 to January 2016 and imaged by OCTA. The resulting OMAG angiograms provided detailed visualization of retinal and choroidal vascular networks presented within the retina and choroid in a large field of view (FOV) (∼6.7 mm × 6.7 mm). All patients with a severity score greater than 3 showed abnormal microvasculature in both deep retinal and choroidal layers on OMAG images. Images of patients with a score of 4 indicating only peripheral abnormalities demonstrated relatively normal vasculature networks. Microvascular changes in the retinal and choroidal vasculature correlate with structural changes in the slab from IS/OS junction to RPE layer. CONCLUSIONS: OCTA is useful in evaluating the microvascular changes in a large FOV encompassing the maculae of patients with RP. The large FOV of OMAG angiograms, enabled by the motion tracking, provides visualization of high definition and high resolution microvascular networks at varying stages of RP. Microvascular imaging may have significant utility in the diagnosis and monitoring of disease progression in RP patients.

Eyelid swelling, an unusual presentation of pneumomediastinum.

An 11-year-old girl with no significant medical or ocular history presented to the emergency department with asymmetrical eyelid swelling for 2 days. She was noted to have eyelid crepitus on examination. The patient reported a prolonged episode of crying followed by chest pain and dyspnea that resolved prior to her presentation. Both face and chest CT showed extensive air tracking in the subcutaneous tissues of the neck and face and pneumomediastinum without pneumothorax. The patient was discharged home without further intervention. On follow-up 1 to 2 weeks later, she had complete resolution of her symptoms. While pneumomediastinum is extremely rare in the pediatric population, it can be considered in the differential diagnoses of eyelid swelling and crepitus in the appropriate context. To this author's knowledge, this is the first pediatric case of pneumomediastinum with an initial presentation of eyelid swelling.

In-vivo characterization of scleral rigidity in myopic eyes using fundus-pulsation optical coherence elastography.

The sclera plays an important role in the structural integrity of the eye. However, as myopia progresses, the elongation of the eyeball exerts stretching forces on the posterior sclera, which typically happens in conjunction with scleral remodeling that causes rigidity loss. These biomechanical alterations can cause localized eyeball deformation and vision impairment. Therefore, monitoring scleral rigidity is clinically important for the management and risk assessment of myopia. In this study, we propose fundus pulsation optical coherence elastography (FP-OCE) to characterize posterior scleral rigidity in living humans. This methodology is based on a choroidal pulsation model, where the scleral rigidity is inversely associated with the choroidal max strain obtained through phase-sensitive optical coherence tomography (PhS-OCT) measurement of choroidal deformation and thickness. Using FP-OCE, we conducted a pilot clinical study to explore the relationship between choroidal strain and myopia severity. The results revealed a significant increase in choroidal max strain in pathologic myopia, indicating a critical threshold beyond which scleral rigidity decreases significantly. Our findings offer a potential new method for monitoring myopia progression and evaluating therapies that alter scleral mechanical properties.

Prevalence, Progression, and Modifiable Risk Factors for Diabetic Retinopathy in Youth and Young Adults With Youth-Onset Type 1 and Type 2 Diabetes: The SEARCH for Diabetes in Youth Study.

OBJECTIVE: To determine the prevalence, progression, and modifiable risk factors associated with the development of diabetic retinopathy (DR) in a population-based cohort of youth-onset diabetes. RESEARCH DESIGN AND METHODS: We conducted a multicenter, population-based prospective cohort study (2002-2019) of youth and young adults with youth-onset type 1 diabetes (n = 2,519) and type 2 diabetes (n = 447). Modifiable factors included baseline and change from baseline to follow-up in BMI z score, waist/height ratio, systolic and diastolic blood pressure z score, and A1C. DR included evidence of mild or moderate nonproliferative DR or proliferative retinopathy. Prevalence estimates were standardized to estimate the burden of DR, and inverse probability weighting for censoring was applied for estimating risk factors for DR at two points of follow-up. RESULTS: DR in youth-onset type 1 and type 2 diabetes is highly prevalent, with 52% of those with type 1 diabetes and 56% of those with type 2 diabetes demonstrating retinal changes at follow-up (mean [SD] 12.5 [2.2] years from diagnosis). Higher baseline A1C, increase in A1C across follow-up, and increase in diastolic and systolic blood pressure were associated with the observation of DR at follow-up for both diabetes types. Increase in A1C across follow-up was associated with retinopathy progression. BMI z score and waist/height ratio were inconsistently associated, with both positive and inverse associations noted. CONCLUSIONS: Extrapolated to all youth-onset diabetes in the U.S., we estimate 110,051 cases of DR developing within ∼12 years postdiagnosis. Tight glucose and blood pressure management may offer the opportunity to mitigate development and progression of DR in youth-onset diabetes.

Giant Intraoperative Corneal Bulla Managed with Bandage Lens Technique During Vitrectomy Surgery.

PURPOSE: To report a case of giant intraoperative corneal bulla formation in a patient with a history of recent phacoemulsification with clear corneal incision that was managed with a bandage contact lens intraoperatively. METHODS: Retrospective case report with anterior segment optical coherence tomography (AS-OCT). RESULTS: A 77-year-old woman with history of recent complicated cataract surgery with retained lens fragments underwent pars plana vitrectomy (PPV) and scleral fixated intraocular lens placement. During PPV, a large corneal bulla formed at the site of the main corneal incision, confirmed with AS-OCT. A bandage contact lens with viscoelastic was used to overcome visualization challenges and safely proceed with the surgery. CONCLUSION: This is the first report of corneal bullae formation during PPV that is confirmed by AS-OCT and successfully managed with a bandage contact lens intraoperatively.

Laser Peripheral Iridotomy Curriculum: Lecture and Simulation Practical.

Introduction: Approximately 20 million people worldwide are affected by primary angle closure glaucoma, which is often treated with a laser peripheral iridotomy (LPI). In the United States, at least 60,000 to 80,000 LPIs are performed annually. However, complications can arise from improperly performed LPIs. While the Accreditation Council for Graduate Medical Education requires that all ophthalmology residents perform at least four primary LPIs prior to graduating, formal training is often lacking. In an effort to standardize LPI teaching, an LPI lecture curriculum and skills practice session were introduced. Methods: A lecture and wet-lab curriculum was developed at the University of Washington to formally teach first-year ophthalmology residents the indications and techniques for LPI. Pre- and postcurriculum knowledge was tested, and LPI performance was assessed by comparing pre- and postcurriculum total number of shots and time needed to successfully complete an LPI on a commercially available model eye. Results: The course was highly rated by 10 residents (all PGY 2), with an increase in pre- versus posttest scores, an improvement in LPI performance metrics, and an increase in pre- versus postcurriculum scores for the three survey questions regarding curriculum objectives. Discussion: This course improved learner knowledge and confidence in performing LPI. Test scores improved following the course, as did self-assessed confidence levels of the residents. Residents made a number of positive comments about the course. We plan to continue holding this training session every year at our institution.

Ultra-Widefield Protocol Enhances Automated Classification of Diabetic Retinopathy Severity with OCT Angiography.

PURPOSE: To assess the diagnostic usefulness of retinal nonperfusion to classify eyes based on diabetic retinopathy (DR) severity on OCT angiography (OCTA) and determine whether wider field of view (FOV) OCTA protocols enhance the diagnostic usefulness of retinal nonperfusion in the classification of DR severity. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: Diabetic patients undergoing ultra-widefield (UWF) OCTA imaging at 1 academic retina practice. METHODS: Ultra-widefield OCTA images with 100° FOV were obtained from 60 eyes. Eyes were grouped as those with diabetes without retinopathy (DWR), those with nonproliferative diabetic retinopathy (NPDR), or those with proliferative diabetic retinopathy (PDR). The ratio of nonperfusion (RNP) was expressed as the percent area of capillary nonperfusion within the FOV. The RNP was obtained in the FOV 100° image and concentric sectors encompassing 10°, 10° to 30°, 30° to 50°, and 50° to 100°. MAIN OUTCOME MEASURES: Mean RNP among DR groups, mean RNP measured among FOV sectors, and area under the curve (AUC) of the receiver operating characteristics when using RNP as a cutoff value to distinguish between DR groups. RESULTS: Mean RNP from the FOV 50° to 100° sector was different among all groups: DWR, 14.6±5.1%; NPDR, 27.5±7.5%; and PDR, 41.5±19.1% (P < 0.01). Within each DR group, field of view from 50° to 100° measured higher RNP than all other sectors (P < 0.01). Field of view from 50° to 100° showed the highest optimal sensitivity and specificity to distinguish NPDR from DWR with an RNP cutoff value of 21.2% (89.5% and 88.2%; AUC, 0.944) and PDR from NPDR with an RNP cutoff value of 31.6% (79.2% and 78.9%; AUC, 0.752). CONCLUSIONS: Ratio of nonperfusion on average is higher in more severe DR. The most peripheral sector of the widefield OCTA (FOV 50°-100°) showed on average higher RNP and showed more diagnostic usefulness in determining DR severity compared with more central sectors and the FOV 100 image as a whole.

Quantitative Handheld Swept-Source Optical Coherence Tomography Angiography in Awake Preterm and Full-Term Infants.

Purpose: To compare retinal vascular parameters acquired by handheld swept-source optical coherence tomography angiography (SS-OCTA) between nonsedated preterm and full-term infants. Methods: Preterm and full-term infants at the University of Washington Medical Center were enrolled. Retinal angiograms (nominal size ∼7 × 7 mm2) were obtained at each routine retinopathy of prematurity (ROP) screening session for preterms and once during the first 72 hours of life for full-terms. Macular vessel area density and nonperfusion area were evaluated on the binarized vasculature map in both small (1.5 × 1.5 mm) and large (3 × 3 mm) quadrants. Average vessel diameter and tortuosity values were obtained from each large vessel branch (length >200 µm). All vascular analyses used previously published algorithms. Results: Handheld SS-OCTA captured 31 of 55 (56%) high-quality volumes on 8 awake preterm infants (gestational age 28 ± 4 weeks, birth weight 891 ± 314 g, postmenstrual age at first imaging session 37 ± 2 weeks) and 48 of 54 (89%) volumes on 12 awake full-term infants (gestational age 39 ± 1 weeks, birth weight 3405 ± 329 g). Signal-to-noise ratio was 5.08 ± 1.52 dB in preterm and 4.90 ± 1.12 dB in full-term infants. Preterm infants had higher mean large vessel tortuosity compared to full-term infants (P = 0.004). The large nasal quadrant vessel area density of infants with stage 3 and/or pre-plus or worse ROP was higher than other preterm infants (P = 0.007). Conclusions: Although inadequate image quality limited usable imaging sessions, handheld SS-OCTA achieved adequate signal-to-noise ratio in nonsedated infants for quantitative retinal vascular parameter analysis. Translational Relevance: Large- and small-vessel parameters were associated with prematurity and ROP severity, respectively.

Microvascular Changes in the Choriocapillaris of Diabetic Patients Without Retinopathy Investigated by Swept-Source OCT Angiography.

Purpose: To investigate the microvascular changes in macular retina and choriocapillaris (CC) in diabetic eyes without retinopathy using swept-source optical coherence tomography angiography (SS-OCTA). Methods: A commercial SS-OCTA system was used to collect 6 × 6-mm macular scans from patients. Three depth-resolved retinal slabs and a CC slab were segmented by a validated semiautomated algorithm. Retinal vessel area density, vessel skeleton density, and nonperfusion area were calculated on segmented retinal slabs. Foveal avascular zone was automatically measured based on en face image of the whole retinal layer. For CC quantification, the percentage of flow deficits (FD%) and the flow deficit (FD) sizes were measured. Results: Sixteen eyes from 16 diabetic patients without clinically detectable retinopathy and 16 eyes from 16 age-matched nondiabetic controls were included. There was no significant difference between the two groups in all retinal vessel quantitative parameters (all P > 0.05). However, the mean FD% and mean FD sizes were significantly increased in CC in the central 1.0-mm disk (P = 0.011 and P = 0.017, respectively), the central 1.5-mm rim (P = 0.003 and P = 0.009, respectively), the central 2.5-mm rim (P = 0.018 and P = 0.020, respectively), and the entire 5.0-mm disk (P = 0.009 and P = 0.008, respectively) in diabetic eyes compared with controls. Conclusions: CC perfusion in the macula is decreased in diabetic patients without retinopathy as compared to age-matched normal controls. Decreased CC perfusion in the macula may be an early indicator of otherwise clinically undetectable diabetic vasculopathy.

PARACENTRAL ACUTE MIDDLE MACULOPATHY ASSOCIATED WITH BILATERAL OPTIC DISK SWELLING AND MENINGITIS.

BACKGROUND/PURPOSE: To present a novel case of paracentral acute middle maculopathy associated with bilateral optic disk swelling. METHODS: Retrospective case report. RESULTS: A 67-year-old woman presented with sudden onset of central vision loss and subsequent bilateral optic disk edema, retinal vessel attenuation, and anterior uveitis. Cerebrospinal fluid analysis showed signs of inflammation. Spectral domain optical coherence tomography demonstrated the pathognomonic hyperreflectivity of the middle retinal layers consistent with paracentral acute middle maculopathy. Swept-source optical coherence tomography angiography with custom vessel analysis demonstrated a 18.3% decrease in the deep retinal vascular density and 2.4 times increase in absent flow area in the affected eye compared with the fellow eye. CONCLUSION: This case demonstrates a novel association between paracentral acute middle maculopathy and bilateral optic disk swelling secondary to central nervous system inflammation and possible infection. Although spectral domain optical coherence tomography is valuable in detecting paracentral acute middle maculopathy, optical coherence tomography angiography with vessel analysis can provide additional insight into the disease mechanism.

Quantitative assessment of choriocapillaris flow deficits in diabetic retinopathy: A swept-source optical coherence tomography angiography study.

PURPOSE: To quantitatively assess choriocapillaris (CC) flow deficits in eyes with diabetic retinopathy (DR) using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: Diabetic subjects with different stages of DR and age-matched healthy subjects were recruited and imaged with SS-OCTA. The en face CC blood flow images were generated using previously published and validated algorithms. The percentage of CC flow deficits (FD%) and the mean CC flow deficit size were calculated in a 5-mm-diameter circle centered on the fovea from the 6×6-mm scans. RESULTS: Forty-five diabetic subjects and 27 control subjects were included in the study. The CC FD% in diabetic eyes was on average 1.4-fold greater than in control eyes (12.34±4.14% vs 8.82±2.61%, P < 0.001). The mean CC FD size in diabetic eyes was on average 1.4-fold larger than in control eyes (2151.3± 650.8µm2 vs 1574.4±255.0 µm2, P < 0.001). No significant difference in CC FD% or mean CC FD size was observed between eyes with nonproliferative DR and eyes with proliferative DR (P = 1.000 and P = 1.000, respectively). CONCLUSIONS: CC perfusion in DR can be objectively and quantitatively assessed with FD% and FD size. In the macular region, both CC FD% and CC FD size are increased in eyes with DR. SS-OCTA provides new insights for the investigations of CC perfusion status in diabetes in vivo.

Retinal Capillary Nonperfusion on OCT-Angiography and Its Relationship to Kidney Function in Patients with Diabetes.

BACKGROUND: Diabetic retinopathy and kidney disease share underlying mechanisms of microvascular damage and are often comorbid in people with diabetes. We evaluated whether there is a relationship between retinal capillary perfusion as measured by swept-source optical coherence tomography angiography and estimated glomerular filtration rate (eGFR) and albuminuria in patients with diabetes and chronic kidney disease (CKD). METHOD: A cross-sectional pilot study was conducted at the University of Washington among a subset of participants with diabetes and CKD participating in a larger cohort study. Participants were excluded if they were known to have kidney disease from conditions other than diabetes. Ten participants (11 eyes) were included. Retinal nonperfusion (RNP) and vessel density (VD) were measured by swept-source optical coherence tomography angiography in 30° and 60° field of view (FOV) regions centered at the fovea. Correlations of RNP and VD with eGFR and albuminuria were analyzed. RESULTS: Participants had a mean age of 72 years, hemoglobin A1c of 8.1%, eGFR of 45 mL/min/1.73 m2, and urine albumin-to-creatinine ratio of 162 mg/g. Mean (SD) RNP was 6.6% (4.2%) and 16.9% (7.7%) in 30° and 60° FOV regions, respectively. eGFR was negatively correlated to RNP in both the 30° and 60° FOV regions (R = -0.69, p=0.004, and R = -0.46, p=0.057, respectively), and correlations were stronger among a subset of 7 participants with evidence of diabetic retinopathy on exam and fundus photos. The estimated GFR was not significantly correlated with vessel density. Urine albumin-to-creatinine ratio was not significantly correlated with RNP or VD. CONCLUSIONS: Our proof-of-concept study showed that lower eGFR was significantly correlated with retinal nonperfusion in participants with diabetes and CKD. Advanced retinal imaging may enhance the noninvasive evaluation of kidney function in diabetes.

Prognostic Utility of Whole-Genome Sequencing and Polymerase Chain Reaction Tests of Ocular Fluids in Postprocedural Endophthalmitis.

PURPOSE: To associate detection of potential pathogen DNA in endophthalmitis with clinical outcomes. DESIGN: Prospective cohort study. METHODS: Patients in whom endophthalmitis was diagnosed following an intraocular procedure were recruited. Clinical outcome data from baseline, week-1, month-1, and month-3 visits were collected. Intraocular biopsy samples were cultured by standard methods. Quantitative polymerase chain reaction (qPCR) was performed for specific pathogens and whole-genome sequencing (WGS). RESULTS: A total of 50 patients (mean age 72 years old; 52% male) were enrolled. Twenty-four cases were culture-positive and 26 were culture-negative. WGS identified the cultured organism in 76% of culture-positive cases and identified potential pathogens in 33% of culture-negative cases. Month-1 and -3 visual acuities did not vary by pathogen-positive versus pathogen-negative cases as detected by either culture or WGS. Visual outcomes of Staphylococcus epidermidis endophthalmitis were no different than those of pathogen-negative cases, whereas the patients infected with other pathogens showed worse outcome. Higher baseline bacterial DNA loads of bacteria other than those of S epidermidis detected by WGS were associated with worse month-1 and -3 visual acuity, whereas the S epidermidis loads did not appear to influence outcomes. Torque teno virus (TTV) and Merkel cell polyomavirus (MCV) were detected by qPCR in 49% and 19% of cases, respectively. Presence of TTV at presentation was associated with a higher rate of secondary pars plana vitrectomy (P = .009) and retinal detachment (P = .022). CONCLUSIONS: The presence and higher load of bacteria other than S epidermidis detected by WGS or DNA from TTV by qPCR in ocular fluids is associated with worse outcomes in post-procedure endophthalmitis.

Handheld swept-source optical coherence tomography with angiography in awake premature neonates.

BACKGROUND: Retinopathy of prematurity (ROP) can lead to retinal detachment and severe vision loss and is a common cause of childhood blindness. Optical coherence tomography angiography (OCTA) is a non-invasive imaging modality that can be used to detect potential abnormalities in the microvasculature in this population. The objective of this study is to assess the feasibility of a newly developed handheld swept source OCT (SS-OCT) device to successfully acquire structural vitreoretinal and retinal microvascular images in awake premature infants. METHODS: OCT and OCTA images were acquired at the time of routine ROP examinations from awake, unsedated preterm infants in the Neonatal Intensive Care Unit using a clinical research prototype handheld probe integrated with an SS-OCT system working at 1,060 nm wavelength and an imaging speed of 200,000 A-scans per second (200 kHz), enabling volume OCT and OCTA scans. Each volume was acquired with approximately 36˚ field of view (~6.3×6.3 mm in infants) in 4.8 s. Quality of acquired OCT and OCTA volume images, microvascular information, and vitreoretinal features were determined by 3-masked grader consensus. RESULTS: Twelve infants (5 females, mean gestational age 28.3 weeks, median birth weight 901 g, stages 0 to 3 ROP) underwent a total of 73 individual eye imaging sessions. High-quality OCT images of the fovea and the optic nerve were present in 69/73 (94.5%) and 56/73 (76.7%) scans, respectively. Vitreous bands were observed in 10/73 (13.7%); punctate hyperreflective vitreous opacities in 47/73 (64.4%); epiretinal membrane (ERM) in 6/73 (8.2%); and cystoid macular edema (CME) in 12/73 (16.4%) scans. Mild vessel elevation was noted in 3/73 (4.1%) images, and severe vessel elevation in 4/73 (5.5%) scans. OCTA images obtained in 8 awake infants revealed good quality images of the foveal microvasculature in 11/19 (58%) eye imaging sessions for 6/8 (75%) infants; and peripapillary microvasculature in 14/19 (74%) eye imaging sessions for 5/8 (63%) infants. CONCLUSIONS: The SS-OCTA handheld device can capture important vitreoretinal characteristics such as peripapillary and foveal microvasculature, as well as hyperreflective punctate vitreous opacities and tractional vitreous bands, which may predict ROP severity. These images were captured in awake, premature infants without the use of direct ocular contact, an eyelid speculum, or sedation.

CAPTCHA as a Visual Performance Metric in Active Macular Disease.

PURPOSE: CAPTCHA (completely automated public turing test to tell computers and humans apart) was designed as a spam prevention test. In patients with visual impairment, completion of this task has been assumed to be difficult; but to date, no study has proven this to be true. As visual function is not well measured by Snellen visual acuity (VA) alone, we theorized that CAPTCHA performance may provide additional information on macular disease-related visual dysfunction. METHODS: This was designed as a pilot study. Active disease was defined as the presence of either intraretinal fluid (IRF) or subretinal fluid (SRF) on spectral-domain optical coherence tomography. CAPTCHA performance was tested using 10 prompts. In addition, near and distance VA, contrast sensitivity, and reading speed were measured. Visual acuity matched pseudophakic patients were used as controls. Primary outcome measures were average edit distance and percent of correct responses. RESULTS: 70 patients were recruited: 33 with active macular disease and 37 control subjects. Contrast sensitivity was found to be significantly different in both the IRF (p < 0.01) and SRF groups (p < 0.01). No significant difference was found comparing the odds ratio of average edit distance of active disease (IRF, SRF) vs. control (OR 1.09 (0.62, 1.90), 1.10 (0.58, 2.05), p=0.77, 0.77) or percent correct responses of active disease vs. control (OR 0.98 (0.96, 1.01), 1.09 (0.58, 2.05), p=0.22, 0.51) in CAPTCHA testing. The goodness of fit using logistic regression analysis for the dependent variables of either IRF or SRF did not improve accounting for average edit distance (p=0.49, p=0.27) or percent correct (p=0.89, p=0.61). CONCLUSIONS: Distance VA and contrast sensitivity are positively correlated with the presence of IRF and SRF in active macular disease. CAPTCHA performance did not appear to be a significant predictor of either IRF or SRF in our pilot study.

Optic Nerve Head Perfusion Before and After Intravitreal Antivascular Growth Factor Injections Using Optical Coherence Tomography-based Microangiography.

PURPOSE: To use optical coherence tomography angiography (OCTA) to evaluate the changes in optic nerve head perfusion following intravitreal antivascular endothelial growth factor injections. METHODS: Preinjection and postinjection intraocular pressure (IOP) and OCTA images were taken of both the injected and uninjected fellow eyes. RESULTS: Mean preinjection IOP was 16.6±4.7 mm Hg, which increased to a mean of 40.3±13.0 mm Hg (P<0.0001) during the first postinjection image and remained elevated at 36.1±11.5 mm Hg (P<0.0001) during the second postinjection image. Although no significant change was observed in flux, vessel area density, or normalized flux when comparing the OCTA preinjection and first postinjection images, a significant decrease at the second postinjection image was observed (P=0.03, 0.02, and 0.03, respectively). No significant change was observed in the uninjected fellow eye during the same time period (P=0.47, 0.37, and 0.38, respectively). CONCLUSIONS: Following an antivascular endothelial growth factor injection, mean IOP increased significantly and OCTA imaging of the optic nerve demonstrated a mild but significant decrease in optic nerve head perfusion parameters. Clinicians performing these injections should be aware of these findings and monitor the status of the optic nerve in patients undergoing injections.

Modulation of Nrf2-dependent antioxidant functions in the RPE by Zip2, a zinc transporter protein.

PURPOSE: To characterize the involvement of Zip2, a zinc transporter protein, in the antioxidant functions of cultured human retinal pigment epithelial (RPE) cells. METHODS: The expression of zinc transporter proteins was determined by RT-PCR. Intracellular zinc concentration was assessed by staining with a zinc-sensitive dye followed by flow cytometry. Stable overexpression of the transporter protein Zip2 was achieved by transducing ARPE-19 cells with a retroviral vector containing the open reading frame of the human Zip2 gene. Activity of nuclear factor erythroid 2-related factor 2 (Nrf2) was measured using a dual luciferase assay after transient transfection of reporter plasmids containing the antioxidant response element (ARE). Glutamate-cysteine ligase (GCL) expression was measured by quantitative real-time RT-PCR. RESULTS: Cultured RPE cells could transport zinc with Zip2 as an influx transporter expressed in ARPE-19 cells and human RPE cells isolated from postmortem donor eyes. The mRNA level of Zip2 was influenced by intracellular and extracellular zinc concentrations. Overexpression of Zip2 resulted in increased Nrf2 activity, higher GCL expression, and increased glutathione synthesis. CONCLUSIONS: RPE cells can actively uptake zinc through the transporter Zip2, and the increased intracellular zinc upregulates the Nrf2-dependent antioxidant function.