Macular Thickness Fluctuations in Eyes With Diabetic Macular Edema Treated With Intravitreal Steroid.

BACKGROUND AND OBJECTIVE: Macular thickness fluctuations (MTF) over time may be more predictive of visual outcomes than absolute macular thickness in patients with diabetic macular edema (DME) treated with anti-vascular endothelial growth factor (anti-VEGF). It is unclear whether this association exists in DME patients treated with intravitreal steroids or whether steroids confer reduced MTF versus anti-VEGF treatments. PATIENTS AND METHODS: MTF was compared before and after initiation of steroids in DME patients treated with intravitreal steroids. A mixed-effects linear regression model was used to determine the association between MTF and best-corrected visual acuity (BCVA). RESULTS: Mean 12-month MTF significantly decreased after steroid initiation (61.1 µm versus 53.5 µm, P = 0.04, n = 105 eyes). Mean BCVA after 12 months was not significantly different from baseline. No significant association between post-steroid MTF and 12-month BCVA was found. CONCLUSION: Steroid treatment decreases MTF while BCVA remains stable in DME patients previously treated with anti-VEGF. [Ophthalmic Surg Lasers Imaging Retina 2023;54:454-460.].

The Incidence, Time to Development, and Risk Factors for Fellow Eye Retinal Vein Occlusions.

BACKGROUND AND OBJECTIVE: Little is known about factors affecting risk or time to development of fellow eye retinal vein occlusion (RVO). The purpose of this study was to examine the incidence and risk factors for fellow eye RVO. PATIENTS AND METHODS: This was a retrospective case-control study comparing unilateral and fellow eye RVO patients. This study was exempt by the Cleveland Clinic Institutional Review Board. RESULTS: Out of 1,083 patients, fellow eye RVO had a cumulative incidence of 3.6% (95% CI 2.61, 4.94) with a median time to development of 18 months (95% CI 6.0, 28.0). Fellow eye disease was associated with multiple characteristics including chronic kidney disease (odds ratio [OR] 3.78, 95% CI 1.89 to 7.55) and diabetic retinopathy (3.18, 1.57 to 6.44). CONCLUSION: While fellow eye RVO is relatively rare, it typically occurs within the first few years following initial diagnosis. Multiple characteristics were associated with fellow eye disease and time to onset. [Ophthalmic Surg Lasers Imaging Retina 2023;54:471-476.].

External Compressive Ischemic Orbitopathy: A Rising Clinical Entity.

PURPOSE: Saturday night retinopathy, the term coined by Jayam et al . in 1974, is a rare condition in which external compression of the orbit during a drug and alcohol stupor causes a unilateral orbitopathy with ophthalmoplegia and ischemic retinopathy. This condition has been increasingly reported in the last decade, correlating with an increasing burden of substance use. This condition mirrors a similar entity typically reported in patients following spinal surgery, where a headrest supporting the patient's face compresses the orbit. The current authors combine these 2 entities, entitled external compressive ischemic orbitopathy, and present a comprehensive literature review describing this entity. METHODS: A systematic review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All related publications of vision loss in the setting of orbital compression were reviewed. Data collected included patient demographics, precipitating circumstances of vision loss, presenting ocular symptoms, outcomes, and ancillary imaging. RESULTS: In total 31 articles were selected for inclusion, yielding 46 patients. A total of 10 patients suffered orbitopathy in the setting of a drug stupor, and 36 following prone-positioned surgery. However, 79% of patients presented with visual acuity of light perception or worse. Also, 86% of patients presented with ophthalmoplegia, 92% with proptosis and orbital edema, and 86% with varying degrees of retinal ischemia. When compared with iatrogenic cases, self-induced stuporous cases demonstrated worse presenting visual acuity, ophthalmoplegia, retinal and choroidal filling, and worse final outcomes. CONCLUSION: External compressive ischemic orbitopathy is a severe vision-threatening condition that has been increasingly reported in the last decade.

Time to fellow eye involvement in patients with unilateral diabetic macular oedema.

OBJECTIVE: To examine the time to onset of disease in the fellow eye of patients with unilateral DMO in routine clinical practice and to identify risk factors for development of bilateral DMO. DESIGN: Retrospective cohort study. PARTICIPANTS: One hundred forty treatment-naive patients 18 years or older with unilateral DMO presenting to Cole Eye Institute between January 2012 and July 2021. METHODS: Records of patients with unilateral DMO were reviewed for development of DMO in the fellow eye. Demographic, diabetic, ocular, and systemic characteristics were collected at initial DMO diagnosis date. Bivariate and multivariate analyses were performed and significant factors were modelled using Kaplan-Meier curves. RESULTS: Fifty patients with conversion to bilateral DMO and 90 patients without conversion were identified. Average time to bilateral DMO was 15.0 ± 15.7 months. 64% of patients converted within 1 year and 90% converted within 3 years. HbA1c (p = 0.003), diabetic retinopathy duration (p = 0.029), and diabetic foot disease (DFD) (p = 0.002) were identified as significant risk factors for conversion. Patients with better visual acuity at time of initial diagnosis and history of panretinal photocoagulation (PRP) (p = 0.044) or focal laser (p = 0.035) in the primary eye were also more likely to convert. CONCLUSIONS: Participants were most likely to develop fellow eye DMO within the first year after initial DMO diagnosis. In routine clinical practice, poor glycaemic control and DFD were risk factors associated with bilateral eye involvement. Clinicians may consider screening the fellow eye of high-risk individuals at each appointment within the first year of diagnosis.

Effect of SPARC Suppression in Mice, Perfused Human Anterior Segments, and Trabecular Meshwork Cells.

Purpose: Secreted protein, acidic and rich in cysteine (SPARC) elevates intraocular pressure (IOP), increases certain structural extracellular matrix (ECM) proteins in the juxtacanalicular trabecular meshwork (JCT), and decreases matrix metalloproteinase (MMP) protein levels in trabecular meshwork (TM) endothelial cells. We investigated SPARC as a potential target for lowering IOP. We hypothesized that suppressing SPARC will decrease IOP, decrease structural JCT ECM proteins, and alter the levels of MMPs and/or their inhibitors. Methods: A lentivirus containing short hairpin RNA of human SPARC suppressed SPARC in mouse eyes and perfused cadaveric human anterior segments with subsequent IOP measurements. Immunohistochemistry determined structural correlates. Human TM cell cultures were treated with SPARC suppressing lentivirus. Quantitative reverse transcriptase polymerase chain reaction (PCR), immunoblotting, and zymography determined total RNA, relative protein levels, and MMP enzymatic activity, respectively. Results: Suppressing SPARC decreased IOP in mouse eyes and perfused human anterior segments by approximately 20%. Histologically, this correlated to a decrease in collagen I, IV, and VI in both the mouse TM and human JCT regions; in the mouse, fibronectin was also decreased but not in the human. In TM cells, collagen I and IV, fibronectin, MMP-2, and tissue inhibitor of MMP-1 were decreased. Messenger RNA of the aforementioned genes was not changed. Plasminogen activator inhibitor 1 (PAI-1) was upregulated in vitro by quantitative PCR and immunoblotting. MMP-1 activity was reduced in vitro by zymography. Conclusions: Suppressing SPARC decreased IOP in mice and perfused cadaveric human anterior segments corresponding to qualitative structural changes in the JCT ECM, which do not appear to be the result of transcription regulation.

Secreted protein acidic and rich in cysteine (SPARC) knockout mice have greater outflow facility.

PURPOSE: Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that regulates intraocular pressure (IOP) by altering extracellular matrix (ECM) homeostasis within the trabecular meshwork (TM). We hypothesized that the lower IOP previously observed in SPARC -/- mice is due to a greater outflow facility. METHODS: Mouse outflow facility (Clive) was determined by multiple flow rate infusion, and episcleral venous pressure (Pe) was estimated by manometry. The animals were then euthanized, eliminating aqueous formation rate (Fin) and Pe. The C value was determined again (Cdead) while Fin was reduced to zero. Additional mice were euthanized for immunohistochemistry to analyze ECM components of the TM. RESULTS: The Clive and Cdead of SPARC -/- mice were 0.014 ± 0.002 µL/min/mmHg and 0.015 ± 0.002 µL/min/mmHg, respectively (p = 0.376, N/S). Compared to the Clive = 0.010 ± 0.002 µL/min/mmHg and Cdead = 0.011 ± 0.002 µL/min/mmHg in the WT mice (p = 0.548, N/S), the Clive and Cdead values for the SPARC -/- mice were higher. Pe values were estimated to be 8.0 ± 0.2 mmHg and 8.3 ± 0.7 mmHg in SPARC -/- and WT mice, respectively (p = 0.304, N/S). Uveoscleral outflow (Fu) was 0.019 ± 0.007 µL/min and 0.022 ± 0.006 µL/min for SPARC -/- and WT mice, respectively (p = 0.561, N/S). Fin was 0.114 ± 0.002 µL/min and 0.120 ± 0.016 µL/min for SPARC -/- and WT mice (p = 0.591, N/S). Immunohistochemistry demonstrated decreases of collagen types IV and VI, fibronectin, laminin, PAI-1, and tenascin-C within the TM of SPARC -/- mice (p < 0.05). CONCLUSIONS: The lower IOP of SPARC -/- mice is due to greater aqueous humor outflow facility through the conventional pathway. Corresponding changes in several matricellular proteins and ECM structural components were noted in the TM of SPARC -/- mice.

Impact of Resident Overnight Duty Hour Changes on Obstetrical Outcomes: A Population-Based Cohort Study.

OBJECTIVE: To determine whether obstetrical patient outcomes have changed following the introduction of restricted resident work hours. METHODS: A population-based retrospective cohort study of the effects of restricted duty hours for residents in July 2013 at three academic hospitals in Toronto, ON using linked health care databases. The study included 6763 deliveries in the 2 years pre-exposure and 5548 deliveries in the 2 years post-exposure. RESULTS: The primary outcome, planned prior to data collection, was a composite index of 29 maternal/fetal outcomes including maternal transfusion/postpartum hemorrhage, maternal infection, fetal mortality, NICU admissions, and surgical/obstetrical complications. There were seven secondary outcomes analysed: NICU admissions; neonatal death; maternal transfusion or postpartum hemorrhage; maternal infection; and three composite measures. A generalized estimating equation model, clustered by institution, was utilized to assess for differences post-intervention. We found no significant differences in baseline demographics between groups. After the implementation of duty hour restrictions, no significant difference was seen in the primary outcome. However, an increased incidence of composite maternal surgical/obstetrical outcomes (OR 1.191; 95% CI 1.037-1.367, P = 0.013) and transfusion/postpartum hemorrhage (OR 1.232; 95% CI 1.074-1.413, P = 0.003) was found. There were no significant differences in other secondary outcomes. CONCLUSION: Since the implementation of resident duty hour restrictions, there was no overall change in patient outcomes. However, there was an increase in surgical/obstetrical complications and transfusion/postpartum hemorrhage. This suggests that duty hour restrictions may not be beneficial to patient outcomes. It highlights the need to further investigate the clinical impact of a change in resident duty hours.

Unusual Perils of Pelvic Organ Prolapse.

BACKGROUND: Prolapse can be treated with expectant management, pessary, or surgery. Although we consider the first two options benign, rare but serious complications can arise. CASE 1: A 64-year-old presented with recurrent grade 4 prolapse. After 6 months of expectant management, she developed a fistula from an ulcerated area of the prolapse into the peritoneal cavity. CASE 2: An 81-year-old who diligently cared for her ring pessary for 18 years presented with a vesicovaginal fistula. CASE 3: An 80-year-old with a longstanding pessary who stopped using vaginal estrogen for 2 years before developing a vesicovaginal fistula. CONCLUSION: Management of prolapse expectantly and with pessaries are effective treatments, especially to avoid surgery, but can present with their own unusual and infrequent complications, such as fistula formation.