Barriers to Implementation of Teleretinal Diabetic Retinopathy Screening Programs Across the University of California.

Aim: To describe barriers to implementation of diabetic retinopathy (DR) teleretinal screening programs and artificial intelligence (AI) integration at the University of California (UC). Methods: Institutional representatives from UC Los Angeles, San Diego, San Francisco, Irvine, and Davis were surveyed for the year of their program's initiation, active status at the time of survey (December 2021), number of primary care clinics involved, screening image quality, types of eye providers, image interpretation turnaround time, and billing codes used. Representatives were asked to rate perceptions toward barriers to teleretinal DR screening and AI implementation using a 5-point Likert scale. Results: Four UC campuses had active DR teleretinal screening programs at the time of survey and screened between 246 and 2,123 patients at 1-6 clinics per campus. Sites reported variation between poor-quality photos (<5% to 15%) and average image interpretation time (1-5 days). Patient education, resource availability, and infrastructural support were identified as barriers to DR teleretinal screening. Cost and integration into existing technology infrastructures were identified as barriers to AI integration in DR screening. Conclusions: Despite the potential to increase access to care, there remain several barriers to widespread implementation of DR teleretinal screening. More research is needed to develop best practices to overcome these barriers.

Retinal and choroidal manifestations of COVID-19.

PURPOSE OF REVIEW: The novel coronavirus disease in 2019 (COVID-19) has a wide range of systemic manifestations. Ocular manifestations are now well recognized, with conjunctivitis being the most common. Posterior segment involvement is uncommon and has mainly been described in case reports. This review provides an overview of the posterior segment involvement of COVID-19. RECENT FINDINGS: Severe acute respiratory syndrome coronavirus 2 affects the retina and the choroid through either direct entry or triggering an indirect inflammatory response. Majority of the retinal findings is a result of microvascular derangement leading to cotton wool spots, intraretinal hemorrhages, paracentral acute middle maculopathy, acute macular neuroretinopathy, or retinal vein occlusions. Rarely, inflammation involving the retina or the choroid, or reactivation of previously quiescent uveitis, can be seen. SUMMARY: It is important to recognize the possible correlation between ophthalmic conditions and COVID-19 as it can aid in diagnosis, management, and mitigation of the disease.

LABORATORY EVALUATION OF INTRAOCULAR SILICONE OIL REMOVED AFTER 23 YEARS IN SITU.

PURPOSE: To report the clinicopathologic correlation and biochemical analysis of silicone oil removed after 23 years in an eye. METHODS: A 63-years-old man with a history of HIV/AIDS and cytomegalovirus retinitis, status post retinal detachment repair with silicone oil at the age of 39 years, presented with several weeks of worse vision. He was found to have a shallow fovea-off tractional retinal detachment. After the silicone oil was removed during retinal detachment repair, it was analyzed by Fourier-transform infrared spectroscopy and gas chromatography with mass spectrometry. RESULTS: In addition to cyclic and linear silicone oil, cholesterol was found in the removed silicone oil, which was not present in unused silicone oil samples. No other chemical alterations were identified in the extracted silicone oil. CONCLUSION: Silicone oil left inside an eye over an extended period may extract lipophilic substances from adjacent tissue, with possible pathophysiologic effects. However, no other major potentially toxic substance was identified from the long-standing silicone oil sample, suggesting relative chemical stability of the tamponade agent over time.

EVALUATION OF SURGICAL FACTORS AFFECTING VITREOUS HEMORRHAGE FOLLOWING PORT DELIVERY SYSTEM WITH RANIBIZUMAB IMPLANT INSERTION IN A MINIPIG MODEL.

PURPOSE: To develop an animal model of vitreous hemorrhage (VH) to explore the impact of surgical parameters on VH associated with insertion of the Port Delivery System with ranibizumab (PDS) implant. METHODS: Ninety eyes from 45 treatment-naive male Yucatan minipigs received PDS implant insertion or a sham procedure. The effect of prophylactic pars plana hemostasis, scleral incision length, scleral cauterization, surgical blade type/size, and viscoelastic usage on postsurgical VH was investigated. RESULTS: Postsurgical VH was detected in 60.0% (54/90) of implanted eyes. A systematic effect on VH was only detected for pars plana hemostasis before the pars plana incision. The percentage of eyes with VH was 96.6% (28/29) among eyes that did not receive prophylactic pars plana hemostasis and 42.4% (24/58) among eyes that did. There was no VH in eyes that received laser ablation of the pars plana using overlapping 1,000-ms spots; pars plana cautery or diathermy was less effective. The majority of all VH cases (83.3% [45/54]) were of mild to moderate severity (involving ≤25% of the fundus). CONCLUSION: In this minipig surgical model of VH, scleral dissection followed by pars plana laser ablation before pars plana incision most effectively mitigated VH secondary to PDS implant insertion.

COMPARISON BETWEEN RELEASABLE SCLERAL BUCKLING AND VITRECTOMY IN PATIENTS WITH PHAKIC PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To compare the efficiency of releasable scleral buckling (RSB) and pars plana vitrectomy (PPV) in the treatment of phakic patients with primary rhegmatogenous retinal detachment. METHODS: The current study was a prospective randomized clinical trial. One hundred and ten eyes from 110 patients with primary rhegmatogenous retinal detachment and proliferative vitreoretinopathy of Grade B or less were included in this study. The patients were randomly allocated into an RSB group and a PPV group. The functional and anatomical success was compared between groups. RESULTS: The primary anatomical success rate (PPV 41/43 [95.35%] and RSB 38/41 [92.68%]) and final anatomical success rate (PPV and RSB 100%) showed a nonsignificant difference. The best-corrected visual acuity, intraocular pressure, and complications were not different between the groups. However, the incidence of cataract progression was higher in the PPV group (26 of 43 [60.47%]) than in the RSB group (4 of 41 [9.76%]) at the 12-month follow-up. The subfoveal choroidal thickness increased significantly in the RSB group 3 months after surgery, but no longer differed at the postoperative 6-month and 12-month follow-ups. The axial length had increased significantly 1 month after surgery, but the difference was no longer significant at 3 months, 6 months, and 12 months. CONCLUSION: The RSB and PPV procedures have the same effects on the functional and anatomical success for patients with phakic primary rhegmatogenous retinal detachment. Nevertheless, based on the few cases of intraocular complications and cataract progression, we believe that the RSB technique should be preferentially recommended.

Comparison between pars plana and anterior endoscopic cyclophotocoagulation for the treatment of glaucoma.

IMPORTANCE: This is the first study to compare the efficacy and safety of endocyclophotocoagulation (ECP) via pars plana (ECP-plus) with ECP via limbus (anterior ECP) for treating glaucoma. BACKGROUND: There is no direct comparison of treatment outcomes between ECP-plus and anterior ECP. DESIGN: Retrospective study. PARTICIPANTS: Fifty-four consecutive patients. METHODS: Fifty-eight eyes from 54 consecutive patients underwent anterior ECP (33 eyes) or ECP-plus (25 eyes) with 2-year follow-up. Linear mixed model was used to analyse the surgical outcomes. MAIN OUTCOME MEASURES: Intraocular Pressure (IOP) was the primary outcome. Secondary outcomes were best-corrected visual acuity, number of glaucoma medications, complications and success rate. RESULTS: Compared to anterior ECP, patients in the ECP-plus group had lower IOP (estimate of effect size [EES] = -3.7 mmHg, P = 0.023) and used fewer number of glaucoma medications (EES = -1.11, P = 0.003), after adjusting for degrees of treatment, preoperative IOP, and presence of combined ECP and phacoemulsification procedure. Patients with ECP-plus achieved a higher success rate at 2 years postoperatively (80% vs 33.3%, P < 0.001). The decrease in IOP between the preoperative and last follow-up visit was greater in the ECP-plus group compared to the anterior ECP group (14.3 mmHg (52%) vs 5.2 mmHg (24%), P = 0.001). There was no significant difference in complication rates between the two groups (28% vs 33%, P = 0.561). CONCLUSIONS AND RELEVANCE: Anterior ECP and ECP-plus have a similar safety profile, and ECP-plus may offer superior IOP control for the management of glaucoma.

Lamellar macular holes: surgical outcome of 106 patients with long-term follow-up.

PURPOSE: To determine long-term results of vitrectomy for lamellar macular holes (LMH). To evaluate how the type of lamellar macular hole (tractional vs. degenerative) and the crystalline lens status might influence visual outcomes. METHODS: We collected data from 106 patients with symptomatic lamellar macular hole that underwent pars plana vitrectomy with membranectomy and internal limiting membrane peeling. Best-corrected visual acuity (BCVA) and optical coherence tomography appearance were determined preoperatively and postoperatively. RESULTS: Most of the lamellar holes were of tractional type (65%). Mean follow-up after surgery was 36 months. Mean BCVA increased from 20/50 to 20/43 at 6 months and 20/33 at last follow-up visit (p < 0.001). Vision improved in 74 (70%), remained stable in 11 (10%), and decreased in 21 (20%) eyes. Subgroup analysis showed that visual acuity significantly increased in the tractional but not in the degenerative forms of LMH. Thirteen eyes lost two or more ETDRS lines after surgery. Preoperative phakic/pseudophakic status influenced the functional outcomes. CONCLUSIONS: Surgery may be effective in some subsets of patients with lamellar macular hole, but postoperative visual loss is not uncommon and prospective controlled studies are warranted.

LABORATORY EVALUATION OF HYPERCOAGULABLE STATES IN PATIENTS WITH CENTRAL RETINAL VEIN OCCLUSION WHO ARE LESS THAN 56 YEARS OF AGE.

PURPOSE: To investigate whether the results of early tests for hypercoagulability are correlated with the development of central retinal vein occlusion risk factors later in life and to evaluate the necessity of these tests in younger patients. METHODS: This was a retrospective, observational case series. From January 1995 to December 2014, 55 patients aged below 56 years with central retinal vein occlusion (CRVO) were enrolled in the study. Laboratory evaluations for homocysteine, activated protein C resistance, protein C activity, protein S activity, antithrombin III activity, antiphospholipid antibodies, and anticardiolipin antibodies were obtained at the onset of CRVO. After 24 to 205 months, the presence of risk factors for CRVO such as hypertension, obesity, hyperlipidemia, diabetes mellitus, sleep apnea, and glaucoma was determined. Bilateral correlation and logistic regression were performed to determine the correlations between the results of the initial laboratory tests and the diagnosis of CRVO risk factors. RESULTS: The median follow-up was 168.5 months. Five patients completed at least 24 months of follow-up, 9 patients completed at least 5 years, and 36 patients completed at least 10 years. Five patients had no or less than 24 months' follow-up. Fourteen of 50 patients (28%) had at least one positive test result at the onset of CRVO. At the end of follow-up, 11 patients had been diagnosed with obesity (22%), 29 with hypertension (58%), 21 with hyperlipidemia (42%), 24 with diabetes (8%), 5 with sleep apnea (10%), and 8 with glaucoma (16%). Among 36 patients with a minimum 10 years' follow-up, 30 (83%) developed at least one common risk factor, and none experienced any thromboembolic events. There were no correlations between test results and the diagnosis of any risk factors in patients with a minimum of 2, 5, or 10 years' follow-up (P > 0.05). CONCLUSION: The results of laboratory tests evaluating hypercoagulability in young patients with CRVO are not correlated with later-developed commonly known risk factors. Many of the common risk factors were present by the end of the study, suggesting that they still remain the core etiology for the disease. The value of the thrombophilic tests is brought into question, as none of the patients demonstrated further clotting or any unusual thrombi with long-term follow-up.

PERIPAPILLARY PACHYCHOROID SYNDROME.

PURPOSE: To describe the features of peripapillary pachychoroid syndrome (PPS), a novel pachychoroid disease spectrum (PDS) entity. METHODS: Medical records of 31 eyes (16 patients) with choroidal thickening associated with intraretinal and/or subretinal fluid in the nasal macula extending from the disk were reviewed (patients with PPS). Choroidal thickness was compared with 2 age-matched cohorts: typical PDS (17 eyes with central serous chorioretinopathy or pachychoroid neovasculopathy) and 19 normal eyes. RESULTS: The patients with PPS were 81% men aged 71 ± 7 years. Peripapillary pachychoroid syndrome eyes displayed thicker nasal versus temporal macular choroids, unlike PDS eyes with thicker temporal macular choroids (P < 0.0001). Peripapillary intraretinal and/or subretinal fluid was often overlying dilated Haller layer vessels (pachyvessels). Fundus autofluorescence and fluorescein angiography illustrated peripapillary pigmentary mottling without focal leakage. Most PPS eyes (70%) exhibited other PDS findings including serous pigment epithelial detachment or gravitational tracks. Indocyanine green angiography illustrated dilated peripapillary pachyvessels and choroidal hyperpermeability. The disk was usually crowded, with edema noted in 4/31 (13%) eyes and mild late fluorescein disk leakage identified in half of the cases. Choroidal folds (77%), short axial lengths (39% less than 23 mm), and hyperopia (86%) were common. CONCLUSION: Peripapillary pachychoroid syndrome is a distinct PDS variant, in which peripapillary choroidal thickening is associated with nasal macular intraretinal and/or subretinal fluid and occasional disk edema. Recognition of PPS is important to distinguish it from disorders with overlapping features such as posterior uveitis and neuro-ophthalmologic conditions.

Riboflavin and ultraviolet A as adjuvant treatment against Acanthamoeba cysts.

BACKGROUND: Experimental studies have shown that the standard dose of riboflavin (R) or R + ultraviolet-A (UVA) as solo treatment are not able to exterminate Acanthamoeba cysts or even trophozoites. The purpose of this study is to determine whether the application of R + UVA can enhance the cysticidal effects of cationic antiseptic agents in vitro. METHODS: The log of either polyhexamethylene biguanide or chlorhexidine minimal cysticidal concentration in solutions containing riboflavin (concentrations 0.1, 0.05 and 0.025%) plus either Acanthamoeba castellanii cysts or Acanthamoeba polyphaga cysts was determined and compared in groups treated with UVA 30 mW/cm(2) for 30 min and in control groups (with no exposure to UVA). A permutation test was used to determine the P value associated with treatment. RESULTS: Regardless of the riboflavin concentration and UVA treatment condition, no trophozoites were seen in plates where the cysts were previously exposed to cationic antiseptic agent concentrations ≥200 µg/mL for Acanthamoeba castellanii samples and ≥100 µg/mL for A. polyphaga samples. There was no statistical evidence that R + UVA treatment was associated with minimal cysticidal concentration (P = 0.82). CONCLUSION: R + UVA in doses up to 10 times higher than recommended for corneal crosslinking does not enhance the cysticidal effect of either polyhexamethylene biguanide or chlorhexidine in vitro.

Correlation of Serial Scleral and Corneal Pneumatonometry.

PURPOSE: To evaluate the usefulness of scleral pneumatonometry as an alternative for corneal measurements of intraocular pressure (IOP) over a broad range of IOPs. DESIGN: Prospective, observational cohort study. PARTICIPANTS: The study was conducted in the University of California, San Francisco, Retina Clinic between August and November 2013 in 33 adult patients (age range, 34-94 years; mean ± standard deviation, 74.1±13.4 years) receiving anti-vascular endothelial growth factor intravitreal injections, which transiently increase IOP. METHODS: Corneal pachymetry and serial corneal and temporal scleral pneumatonometry (baseline, immediately after, and 10, 20, and 30 minutes after injection) were collected. One-time baseline corneal and scleral pneumatonometry readings were obtained in the noninjected eye. MAIN OUTCOME MEASURES: Correlation analysis and a Bland-Altman plot were used to evaluate reliability and agreement between scleral and corneal measurements of IOP. A linear mixed model was used to determine the relationship between measurements and to perform covariate analyses. RESULTS: Scleral and corneal pneumatonometry showed nearly 1:1 linear correlation, although scleral pneumatonometry was biased toward higher values (r = 0.94; P < 0.001). Scleral pneumatonometry averaged 9.0 mmHg higher than corneal pneumatonometry (95% limits of agreement, -1.5 to 19.5 mmHg). A linear mixed model resulted in the following equation: corneal IOP = 1.04 × scleral IOP - 10.37. Age, central corneal thickness, laterality, and glaucoma and lens status did not impact this relationship. The difference between corneal and scleral pneumotonometry was correlated between the two eyes of individual patients (r = 0.75; P < 0.001). CONCLUSIONS: Differences between serial scleral measurements reflect differences between serial corneal measurements. Scleral pneumatonometry should be considered as an alternative to corneal pneumatonometry for following patients in whom corneal measurements are unreliable or unobtainable.

Vitreous Biomarkers for Proliferative Vitreoretinopathy Prognostication in Patients Undergoing Primary Retinal Detachment Repair.

Purpose: To compare baseline levels of exploratory biomarkers in the vitreous fluid of patients with primary retinal detachment who subsequently develop proliferative vitreoretinopathy (PVR) versus those who do not. Methods: In this exploratory case-control study, we evaluated the baseline protein biomarker levels from a biobank containing the vitreous fluid of patients who had undergone primary pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment. Undiluted samples were collected at the time of PPV and stored at -80°C. Samples from 13 patients who developed PVR within 6 months (PVR group) and 13 age- and gender-matched controls who did not develop PVR (control group) were included. Protein abundance levels were evaluated using a proximity extension assay, and a confirmatory enzyme-linked immunosorbent assay (ELISA) was used to measure the concentration of vimentin. Results: Baseline vimentin (Normalized Protein eXpression [NPX], 8.6 vs. 6.4, P < 0.0001) and heme oxygenase 1 (NPX 8.9 vs. 7.0, P < 0.001) levels were found to be elevated in vitreous fluid of patients who subsequently developed PVR compared to those who did not. Confirmatory analysis using ELISA demonstrated mean vimentin concentrations of 7254 vs. 2727 ng/mL in the PVR versus control groups (P = 0.0152). The odds ratio for developing PVR was 14 (confidence interval, 1.4-168; P = 0.03), assuming a baseline vimentin threshold of 7500 ng/mL. Conclusions: Vimentin is an intermediate filament protein expressed by retinal glial cells, and our data combined with prior evidence suggest that it may serve as an early vitreous biomarker for subsequent PVR formation and reactive gliosis. Furthermore, we found, for the first time, elevated baseline levels of heme oxygenase 1, a measurable indicator of oxidative stress. Translational Relevance: Our positive findings could impact clinical care for retinal detachment patients by facilitating risk stratification for targeted interventions or closer monitoring in those at the highest risk of developing PVR.

Feasibility demonstration of a device for vitreous liquid biopsy incidental to intravitreal injection.

PURPOSE: VitreoDx is an experimental device enabling push-button collection of a neat vitreous liquid biopsy incidental to an intravitreal injection. We explored the ability of the device to collect a sample usable for proteomic biomarker discovery and testing. DESIGN: Pilot study using ex vivo human eyes. METHODS: Non-vitrectomized, human eyes from nine donors 75-91 years of age were refrigerated in BSS and used within 5 days of death. Four VitreoDx devices fitted with 25G needles, and four staked needle insulin syringes with 30G needles, were inserted at equal intervals through the pars plana of each eye and held in place by a fixture. The sampling mode of each VitreoDx device was triggered to attempt to acquire a liquid biopsy up to 70 µL. The plunger of each insulin syringe was retracted to attempt to obtain a liquid biopsy with a maximum volume of 50 µL. Samples acquired with the VitreoDx were extracted to polypropylene cryovials, refrigerated to -80 ºC, and sent for offsite proteomic analysis by proximity extension assay with a focus on panels containing approved and pipelined drug targets for neovascular disease and inflammatory factors. RESULTS: Of the attempted liquid biopsies with the novel 25G VitreoDx, 92% (66 of 72) resulted in successful acquisition (>25 µL) while 89% (64 of 72) attempted by a traditional 30G needle resulted in a successful acquisition. Sample volume sufficient for proteomics array analysis was acquired by the VitreoDx for every eye. Detectable protein was found for 151 of 166 unique proteins assayed in at least 25% of eyes sampled by VitreoDx. CONCLUSIONS: The high acquisition rate achieved by the prototype was similar to that achieved in previous clinical studies where a standard syringe was used with a 25G needle to biopsy vitreous fluid directly prior to standard intravitreal injection. Successful aspiration rates were likewise high for 30G needles. Together, these suggest that it is possible to routinely acquire liquid vitreous biopsies from patients who typically receive intravitreal injections with an injection device using a standard size needle without a vitreous cutter. Protein analysis shows that proteins of interest survive the sampling mechanism and may have potential to direct care in the future.

Race/Ethnicity Analysis of Vascular Alterations in Optical Coherence Tomography Angiography in Diabetic Patients.

PURPOSE: Racial and ethnic minorities have a higher prevalence of diabetic retinopathy (DR) and present at advanced stages of disease. In an urban hospital population, we investigated microvascular differences in optical coherence tomography angiography (OCTA) between racial/ethnic groups while adjusting for socioeconomic status (SES). METHODS: 3 × 3 mm2 macular OCTA scans were obtained for analysis of foveal avascular zone (FAZ) area, FAZ perimeter as well as superficial (SCP) and deep capillary plexus (DCP) vessel density (VD), vessel length density (VLD), and adjusted flow index (AFI). SES was measured using the Area Deprivation Index. Multivariable regression models were used to adjust estimates for relevant confounders. RESULTS: 217 non-diabetic and 1,809 diabetic patients were included in the study, consisting of 42.2% Hispanic, 24.9% non-Hispanic (NH) Asian, 6.8% NH Black, 9.7% NH White and 16.3% Other patients. NH White was used as the reference group. Hispanic, NH Asian, and NH Black patients had significantly greater FAZ areas and FAZ perimeters, and lower DCP VD and VLD, among both non-diabetic and diabetic patients (Benjamini-Hochberg adjusted P-values <0.05). The addition of SES scores in the models did not modify any regressions significantly. CONCLUSIONS: In patients with and without diabetes, racial and ethnic minorities have significant retinal microvasculature differences when compared to NH White patients, regardless of SES. These differences are pronounced in DCP and may predispose racial/ethnic minorities to worse outcomes in DR, thus widening disparities in ophthalmic care.

Bilaterally subluxed diffractive intraocular lenses: big expectations and even bigger comorbidities.

A 78-year-old woman with an ocular history of cataract surgery with a diffractive intraocular lens (IOL) in each eye has developed fluctuating vision, greater in the right eye than the left eye, after 4 years. She has a history of inactive central serous retinopathy and a vision potential of 20/25 + 2 in the right eye and 20/25 in the left eye. She has well-controlled diabetes, hypertension, and hypercholesterolemia. She has enjoyed her spectacle independence for some time and wishes to have her vision restored. On examination, her uncorrected distance visual acuity (UDVA) was 20/50 in the right eye and 20/25 in the left eye and her uncorrected near visual acuity (UNVA) was J3 in the right eye and J1 in the left eye. Intraocular pressures (IOPs) measured 22 mm Hg in the right eye and 18 mm Hg in the left eye. Pupils had limited reactivity with irregularity in the right eye but no obvious relative afferent pupillary defect. Motility and confrontation visual fields were unremarkable in both eyes. Retinal acuity meter was 20/20 in both eyes, and manifest refraction was plano -1.25 × 105 20/40, J3 in the right eye and +0.50 × 20/25, J1 in the left eye. Pertinent findings on slitlamp examination included temporal iris atrophy and transillumination defects greater in the right eye than the left eye, peripupillary pseudoexfoliative changes in both eyes, significant inferior subluxation of a diffractive 3-piece posterior chamber IOL in the capsular bag with lens-pitting peripherally and few central, moderate pseudophacodonesis, and an open posterior capsule in the right eye. In the left eye, she had mild inferior subluxation of a single-piece acrylic diffractive IOL in the capsular bag with moderate pseudophacodonesis and an open posterior capsule (Figure 1JOURNAL/jcrs/04.03/02158034-202403000-00019/figure1/v/2024-02-20T193212Z/r/image-tiff). All other anterior segment findings were unremarkable. On dilated posterior examination, she had a cup-to-disc ratio of 0.50 in the right eye and 0.65 in the left eye without edema hemorrhage or pallor. There were attenuated vessels in both eyes, posterior vitreous detachment in both eyes, and a few small drusen peripherally in both eyes. There was retinal pigment epithelium irregularity and dropout parafoveal in the right eye and subfoveal in the left eye (Figure 2). There was no evidence of macular edema, subretinal fluid, choroidal thickening, or neovascular membranes. The periphery was unremarkable in both eyes.JOURNAL/jcrs/04.03/02158034-202403000-00019/figure2/v/2024-02-20T193212Z/r/image-tiff What testing would you obtain preoperatively to help guide your decision-making? How would you counsel the patient regarding comorbid conditions and expectations?

Microvascular disease not type 2 diabetes is associated with increased cortical porosity: A study of cortical bone microstructure and intracortical vessel characteristics.

Introduction: Fracture risk is elevated in type 2 diabetes (T2D) despite normal or even high bone mineral density (BMD). Microvascular disease (MVD) is a diabetic complication, but also associated with other diseases, for example chronic kidney disease. We hypothesize that increased fracture risk in T2D could be due to increased cortical porosity (Ct.Po) driven by expansion of the vascular network in MVD. The purpose of this study was to investigate associations of T2D and MVD with cortical microstructure and intracortical vessel parameters. Methods: The study group consisted of 75 participants (38 with T2D and 37 without T2D). High-resolution peripheral quantitative CT (HR-pQCT) and dynamic contrast-enhanced MRI (DCE-MRI) of the ultra-distal tibia were performed to assess cortical bone and intracortical vessels (outcomes). MVD was defined as ≥1 manifestation including neuropathy, nephropathy, or retinopathy based on clinical exams in all participants. Adjusted means of outcomes were compared between groups with/without T2D or between participants with/without MVD in both groups using linear regression models adjusting for age, sex, BMI, and T2D as applicable. Results: MVD was found in 21 (55 %) participants with T2D and in 9 (24 %) participants without T2D. In T2D, cortical pore diameter (Ct.Po.Dm) and diameter distribution (Ct.Po.Dm.SD) were significantly higher by 14.6 µm (3.6 %, 95 % confidence interval [CI]: 2.70, 26.5 µm, p = 0.017) and by 8.73 µm (4.8 %, CI: 0.79, 16.7 µm, p = 0.032), respectively. In MVD, but not in T2D, cortical porosity was significantly higher by 2.25 % (relative increase = 12.9 %, CI: 0.53, 3.97 %, p = 0.011) and cortical BMD (Ct.BMD) was significantly lower by -43.6 mg/cm3 (2.6 %, CI: -77.4, -9.81 mg/cm3, p = 0.012). In T2D, vessel volume and vessel diameter were significantly higher by 0.02 mm3 (13.3 %, CI: 0.004, 0.04 mm3, p = 0.017) and 15.4 µm (2.9 %, CI: 0.42, 30.4 µm, p = 0.044), respectively. In MVD, vessel density was significantly higher by 0.11 mm-3 (17.8 %, CI: 0.01, 0.21 mm-3, p = 0.033) and vessel volume and diameter were significantly lower by -0.02 mm3 (13.7 %, CI: -0.04, -0.004 mm3, p = 0.015) and - 14.6 µm (2.8 %, CI: -29.1, -0.11 µm, p = 0.048), respectively. Conclusions: The presence of MVD, rather than T2D, was associated with increased cortical porosity. Increased porosity in MVD was coupled with a larger number of smaller vessels, which could indicate upregulation of neovascularization triggered by ischemia. It is unclear why higher variability and average diameters of pores in T2D were accompanied by larger vessels.

METformin for the MINimization of Geographic Atrophy Progression (METforMIN): A Randomized Trial.

Purpose: Metformin use has been associated with a decreased risk of age-related macular degeneration (AMD) progression in observational studies. We aimed to evaluate the efficacy of oral metformin for slowing geographic atrophy (GA) progression. Design: Parallel-group, multicenter, randomized phase II clinical trial. Participants: Participants aged ≥ 55 years without diabetes who had GA from atrophic AMD in ≥ 1 eye. Methods: We enrolled participants across 12 clinical centers and randomized participants in a 1:1 ratio to receive oral metformin (2000 mg daily) or observation for 18 months. Fundus autofluorescence imaging was obtained at baseline and every 6 months. Main Outcome Measures: The primary efficacy endpoint was the annualized enlargement rate of the square root-transformed GA area. Secondary endpoints included best-corrected visual acuity (BCVA) and low luminance visual acuity (LLVA) at each visit. Results: Of 66 enrolled participants, 34 (57 eyes) were randomized to the observation group and 32 (53 eyes) were randomized to the treatment group. The median follow-up duration was 13.9 and 12.6 months in the observation and metformin groups, respectively. The mean ± standard error annualized enlargement rate of square root transformed GA area was 0.35 ± 0.04 mm/year in the observation group and 0.42 ± 0.04 mm/year in the treatment group (risk difference = 0.07 mm/year, 95% confidence interval = -0.05 to 0.18 mm/year; P = 0.26). The mean ± standard error decline in BCVA was 4.8 ± 1.7 letters/year in the observation group and 3.4 ± 1.1 letters/year in the treatment group (P = 0.56). The mean ± standard error decline in LLVA was 7.3 ± 2.5 letters/year in the observation group and 0.8 ± 2.2 letters/year in the treatment group (P = 0.06). Fourteen participants in the metformin group experienced nonserious adverse events related to metformin, with gastrointestinal side effects as the most common. No serious adverse events were attributed to metformin. Conclusions: The results of this trial as conducted do not support oral metformin having effects on reducing the progression of GA. Additional placebo-controlled trials are needed to explore the role of metformin for AMD, especially for earlier stages of the disease. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Rapid pre-retinal ossification presenting as a vascularized lesion over an area of chronic retinal detachment.

Purpose: To describe the clinical, optical coherence tomography (OCT), and histopathological findings of a patient who was found to have ossification of a pre-retinal membrane after multiple surgical repairs for retinal detachment. Methods: The patient had comprehensive ophthalmic examinations during seven years of follow-up and underwent surgical removal of her pre-retinal membrane. Results: A 24-year-old woman with a history of retinal detachment and multiple retina surgeries presented with baseline vision of 20/200 and refractory glaucoma in the left eye (right eye with no light perception due to prior failed retinal detachment repair). OCT showed a thick epiretinal membrane with hypo-reflective intraretinal spaces in the macula, and exam revealed a chronic retinal detachment superotemporally surrounded by laser barricade. She was stable for six years and then experienced vision loss and decreasing eye pressure, concurrent with rapid evolution of pre-retinal fibrosis, leading to a vascularized consolidation in the mid-periphery, for which she underwent vitrectomy and membrane peel. The vascularized lesion over the area of detachment in the superotemporal retina was removed en bloc through the anterior chamber. Pathological findings revealed woven bone formation anterior to the internal limiting membrane, and the tissue was GFAP negative. Conclusions: Our case adds to the limited knowledge of the chronology, presentation, and surgical management of intraocular ossification, especially of the rarer pre-retinal type. Our patient highlights that development of ossification can happen more quickly than previously thought (year or years rather than decades), can be hidden under vascularized lesions, and is dynamic, with simultaneous release of traction in one area and increased traction in another. Diligent follow-up is indicated even in cases of vitreous membranes from retinal detachment that otherwise appear to have been stable for years.