Imaging and Biomarkers in Diabetic Macular Edema and Diabetic Retinopathy.

PURPOSE OF REVIEW: Diabetic retinopathy (DR) is the leading cause of acquired vision loss in adults across the globe. Early identification and treatment of patients with DR is paramount for vision preservation. The aim of this review paper is to outline current and new imaging techniques and biomarkers that are valuable for clinical diagnosis and management of DR. RECENT FINDINGS: Ultrawide field imaging and automated deep learning algorithms are recent advancements on traditional fundus photography and fluorescein angiography. Optical coherence tomography (OCT) and OCT angiography are techniques that image retinal anatomy and vasculature and OCT is routinely used to monitor response to treatment. Many circulating, vitreous, and genetic biomarkers have been studied to facilitate disease detection and development of new treatments. Recent advancements in retinal imaging and identification of promising new biomarkers for DR have the potential to increase detection, risk stratification, and treatment for patients with DR.

Dacryoadenitis Caused by Blastomycosis: A Case Report.

This is the first case of histopathologically proven blastomycosis involving the lacrimal gland. A 51-year-old woman with a history of disseminated blastomycosis involving her lungs and skin, on oral itraconazole, presented with 3 days of right upper eyelid swelling, erythema, and pain concerning for recurrent dacryoadenitis. MRI showed enlargement of the right lacrimal gland with a cystic lesion at the anterior aspect of the gland with a radiographic differential diagnosis of abscess versus cyst. After no improvement with intravenous antibiotics, orbitotomy with lacrimal gland biopsy and incision and drainage of the cystic lesion were performed. Culture and pathology of the drained fluid demonstrated an abscess with both viable and nonviable broad-based budding yeast consistent with partially treated blastomycosis. The patient's symptoms improved after the surgery and continued itraconazole therapy.

Prospective Study of Canaloplasty and Trabeculotomy Performed by Trainees.

Purpose: To evaluate outcomes of new adopters of the OMNI® Surgical System (Sight Sciences, Inc.) by prospectively evaluating intermediate-term outcomes of patients operated by trainees. Patients and Methods: This was a prospective study of surgeries performed by trainees on patients with open angle glaucoma undergoing simultaneous cataract surgery and ab interno canaloplasty and trabeculotomy using the OMNI Surgical System. Pre-operative intraocular pressure (IOP) and number of glaucoma medications were recorded. Only patients with a minimum of 6-month follow up were included. Baseline IOP was used to separate subjects into two groups: Group 1 (IOP ≥18 mmHg) and Group 2 (IOP <18 mmHg). Mean decrease in IOP and medications was calculated and compared with paired t-tests for the overall sample as well as the subgroups. Success was defined as those with a ≥20% reduction from pre-operative IOP or with an IOP ≤18 mmHg and ≥6 mmHg and on the same or fewer number of medications while not requiring additional surgery. Adverse events were also recorded. Results: Forty-two eyes of 31 patients were included. Mean pre-operative IOP was 17.2 ± 4.8 mmHg and mean number of medications was 2.4 ± 1.2. The primary endpoint was reached in 83.3% of patients at 12 months. IOP was reduced by 22.3% to 13.4 ± 2.4 (p<0.001). Mean number of medications decreased to 1.7 ± 1.6 (p<0.001). Group 1 mean IOP decreased 35.4% from 22.2 ± 4.6 mmHg to 14.3 ± 2.8 mmHg (p<0.001). Group 2 mean number of medications decreased from 2.3 ± 1.1 to 1.6 ± 1.5 (p<0.001). Conclusion: When operated on by the novice MIGS surgeon, the OMNI device provides effective IOP and glaucoma medication reduction with minimal adverse events. Efficacy and safety of the device in the hands of trainees was comparable to experienced glaucoma surgeons suggesting its ease of adoption.

Comparison of Superior versus Inferior Canaloplasty and Trabeculotomy Using the OMNI Surgical System.

Purpose: To compare outcomes of ab-interno canaloplasty and trabeculotomy of the superior versus inferior angle. Patients and methods: This was a prospective, non-randomized, interventional comparison study done at the Veteran Affairs Hospital in Long Beach, California. All patients underwent cataract surgery with intraocular lens implantation combined with ab-interno canaloplasty and trabeculotomy with the OMNI Surgical System (SightSciences, Menlo Park, CA, USA), either superiorly or inferiorly. Pre- and post-operative intraocular pressure using Goldmann applanation tonometry and best corrected visual acuity were obtained and compared using paired t-tests. Patients were excluded if they had any prior intraocular surgery or prior laser trabeculoplasty procedures. Results: 38 eyes from 29 patients were analyzed. 19 eyes were included in the superior group and 19 eyes in the inferior group. Mean pre-operative IOP in the superior group was 17.6 ± 5.2 mmHg and in the inferior group was 17.6 ± 4.6 mmHg (p > 0.99). At 12 months, mean postoperative IOP for the superior group decreased 24% to 13.3 ± 2.8 mmHg while the inferior group decreased 26% to 13.1 ± 2.2 mmHg (p = 0.92). Mean preoperative medications in the superior group were 2.2 ± 1.3 and in the inferior group was 2.4 ± 1.3 (p = 0.88). At 12 months, this decreased to 1.3 ± 1.5 post-operatively in the superior group and 2.2 ± 1.6 post-operatively in the inferior group (p = 0.64). Conclusion: There was no statistical difference in efficacy between superior versus inferior canaloplasty/trabeculotomy with OMNI. Therefore, surgeons can perform the procedure in the direction that is most comfortable for them without affecting outcomes.

Primary Versus Salvage Reverse Total Shoulder Arthroplasty for Displaced Proximal Humerus Fractures in the Elderly: A Systematic Review and Meta-analysis.

BACKGROUND: There is currently no established consensus on best treatment for complex proximal humerus fractures (PHFs) in the elderly. Reverse total shoulder arthroplasty (RTSA) is a viable option in this population but many times is used as a salvage procedure. METHODS: A systematic review of studies comparing RTSA as a primary treatment for PHF versus as a salvage procedure following failed open reduction internal fixation (ORIF), humeral intramedullary nailing, hemiarthroplasty (HA) or non-operative treatment was conducted using PRISMA guidelines. Pooled outcomes and sub-group analyses assessing range of motion, patient reported outcomes and complications were examined using RevMan. RESULTS: Five articles were included in final analysis with 104 patients in the primary RTSA group and 147 in the salvage RTSA group compromising 251 total patients. Primary RTSA had a statistically significant advantage in range of motion (forward flexion and external rotation), patient reported outcomes, and complications compared to salvage RTSA. CONCLUSIONS: Based on the best available evidence, primary RTSA may result in slightly better patient reported outcomes, range of motion and a lower rate of complication when compared to salvage RTSA. Further high-quality prospective studies are needed to confirm the findings of the current review.

Superficial capillary perfusion on optical coherence tomography angiography differentiates moderate and severe nonproliferative diabetic retinopathy.

PURPOSE: To identify objective optical coherence tomography angiography (OCTA) parameters that characterize the spectrum of non-proliferative diabetic retinopathy (NPDR), especially those that distinguish moderate from severe NPDR. METHODS: Sixty eyes of 60 patients with treatment-naïve NPDR (mild: 21, moderate: 21, severe: 18), 23 eyes with diabetes and no retinopathy, and 24 healthy control eyes were enrolled. OCTA slabs were segmented into superficial (SCP), middle (MCP), and deep capillary plexus (DCP) and thresholded by a new method based on DCP skeletonized vessel length. The foveal avascular zone (FAZ) area, parafoveal vessel density (VD), and adjusted flow index (AFI) from all three capillary layers and the vessel length density (VLD) of the SCP were compared between each severity group, after adjusting for age and image quality. RESULTS: All vessel density markers decreased with increasing severity of NPDR. SCP VD and VLD demonstrated significant differences between eyes with diabetes with no retinopathy and mild NPDR (p = 0.001 and p < 0.001, respectively), as well as between moderate vs. severe NPDR (p = 0.004 and p = 0.009, respectively). MCP VD significantly decreased between moderate and severe NPDR (p = 0.01). AFI significantly increased in the SCP and showed a decreasing trend in the MCP and DCP with increasing NPDR severity. CONCLUSIONS: Changes in the SCP VD, SCP VLD, and MCP VD can distinguish severe NPDR from lower-risk stages. SCP changes may be more reliable due to their lower susceptibility to noise and projection artifacts. Thresholding OCTA images based on DCP skeletonized vessel length showed less variability in moderate and severe NPDR. Additional studies are warranted to validate this new thresholding method.

Acute Hyperglycemia Reverses Neurovascular Coupling During Dark to Light Adaptation in Healthy Subjects on Optical Coherence Tomography Angiography.

Purpose: To test the hypothesis that hyperglycemia perturbs neurovascular\ coupling and compromises retinal vascular response during transition from dark to light in healthy subjects using optical coherence tomography angiography (OCTA). Methods: Ten eyes of 10 healthy subjects were tested, first during fasting and then after receiving a 75-g oral glucose solution. In both sessions, OCTA imaging was done in the dark-adapted state and at 50 seconds, 2 minutes, 5 minutes, and 15 minutes of ambient light. Parafoveal vessel density (VD) and adjusted flow index (AFI) were calculated for the superficial capillary plexus (SCP), middle capillary plexus (MCP), and deep capillary plexus (DCP), and vessel length density was calculated for the SCP. These measurements were compared among conditions after adjusting for age, refractive error, and OCTA scan quality. Results: Hyperglycemia leads to a complete reversal of dark/light adaptation trends in VD and AFI in all layers of the inner retina. In the dark, there is significantly decreased VD in the DCP in hyperglycemia. With a transition to light in hyperglycemia, we observed decreased VD in the SCP, increased vessel density in the MCP and DCP, and decreased AFI in all three layers. Conclusions: Our results show that hyperglycemia significantly disrupts neurovascular coupling in healthy eyes, with potential metabolic deficits affecting photoreceptor oxygen demands during dark adaptation and the inner retina during light exposure. In pathological states, such as diabetic retinopathy, where the vasculature is already attenuated, retinal neurons may be exquisitely vulnerable to intermittent hyperglycemic challenge, which should be the focus of future studies.

Reversed Neurovascular Coupling on Optical Coherence Tomography Angiography Is the Earliest Detectable Abnormality before Clinical Diabetic Retinopathy.

Diabetic retinopathy (DR) has traditionally been viewed as either a microvasculopathy or a neuropathy, though neurovascular coupling deficits have also been reported and could potentially be the earliest derangement in DR. To better understand neurovascular coupling in the diabetic retina, we investigated retinal hemodynamics by optical coherence tomography angiography (OCTA) in individuals with diabetes mellitus (DM) but without DR (DM no DR) and mild non-proliferative DR (mild NPDR) compared to healthy eyes. Using an experimental design to monitor the capillary responses during transition from dark adaptation to light, we examined 19 healthy, 14 DM no DR and 11 mild NPDR individuals. We found that the only structural vascular abnormality in the DM no DR group was increased superficial capillary plexus (SCP) vessel density (VD) compared to healthy eyes, while mild NPDR eyes showed significant vessel loss in the SCP at baseline. There was no significant difference in inner retinal thickness between the groups. During dark adaptation, the deep capillary plexus (DCP) VD was lower in mild NPDR individuals compared to the other two groups, which may leave the photoreceptors more susceptible to ischemia in the dark. When transitioning from dark to ambient light, both diabetic groups showed a qualitative reversal of VD trends in the SCP and middle capillary plexus (MCP), with significantly decreased SCP at 5 min and increased MCP VD at 50 s compared to healthy eyes, which may impede metabolic supply to the inner retina during light adaptation. Mild NPDR eyes also demonstrated DCP dilation at 50 s and 5 min and decreased adjusted flow index at 5 min in light. Our results show altered neurovascular responses in all three macular vascular plexuses in diabetic subjects in the absence of structural neuronal changes on high resolution imaging, suggesting that neurovascular uncoupling may be a key mechanism in the early pathogenesis of DR, well before the clinical appearance of vascular or neuronal loss.

Caffeine Delays Retinal Neurovascular Coupling during Dark to Light Adaptation in Healthy Eyes Revealed by Optical Coherence Tomography Angiography.

Purpose: The purpose of this study was to investigate the acute effects of caffeine on retinal hemodynamics during dark to light adaptation using optical coherence tomography angiography (OCTA). Methods: Thirteen healthy individuals (13 eyes) underwent OCTA imaging after dark adaptation and at repeated intervals during the transition to ambient light in two imaging sessions: control and after ingesting 200 mg of caffeine. We analyzed the parafoveal vessel density (VD) and adjusted flow index (AFI) of the superficial capillary plexus (SCP), middle capillary plexus (MCP), and deep capillary plexus (DCP), as well as the vessel length density (VLD) of the SCP. After adjusting for age, refractive error, and scan quality, we compared parameters between control and caffeine conditions. Results: In the dark, MCP VD decreased significantly after caffeine (-2.63 ± 1.28%). During the transition to light, initially, DCP VD increased (12.55 ± 2.52%), whereas SCP VD decreased (-2.09 ± 0.91%) significantly with caffeine compared to control. By 15 minutes in light, DCP VD reversed and was significantly decreased (-5.45 ± 2.62%), whereas MCP VD increased (4.65 ± 1.74%). There were no differences in AFI or VLD. Conclusions: We show that, overall, caffeine causes a trend of delayed vascular response in all three macular capillary plexuses in response to ambient light. Whereas the MCP is constricted in the dark, during the transition from dark to light, there is initially delay followed by prolonged constriction of the DCP and constriction followed by slow dilation of the SCP. We posit that these delayed vascular responses may present potential risk of capillary ischemia.