Telemedicine in Oculoplastic Surgery During the COVID-19 Pandemic: A Single Center Experience.

Purpose: To investigate patterns in oculoplastic surgery telemedicine visits at our institution during the pandemic period. Methods: Retrospective chart review of all patients who had a virtual consultation with the oculoplastic surgery service at Mayo Clinic Rochester between March 1, 2020, and March 1, 2021. Results: There were a total of 148 patients. Mean age was 65 years (95% confidence interval [CI]: 62-68). The mean driving distance to the medical center was 468 kilometers (95% CI: 352-586) and 15 (10%) patients came from states with no practicing American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) members. Out of the 205 virtual visits, 35 (17%) were new, 45 (22%) were return, and 125 (61%) were postoperative. Conversion rate to surgery was 60%. A comparison between type of virtual visits (new vs. return vs. postoperative) revealed that a diagnosis of eyelid malposition was most frequent in postoperative visits (p = < 0.001), skin malignancy was most frequent in new visits (p = 0.009), and orbital tumors (p = 0.018) and thyroid eye disease (p = < 0.001) were most frequent in return visits. Most virtual encounters had supportive media attached including external photographs in 127 (62%) visits and other imaging or testing in 18 (9%) visits. The average virtual visit lasted 18 min (95% CI: 14-22) with technical difficulties noted in 9 (4%) visits. Unanticipated conversion to in-person visits was noted in three (1%) cases. Conclusions: A wide range of oculoplastic surgery conditions was managed virtually during the COVID-19 pandemic. Utilization of initial virtual visit versus follow-up care varied by diagnosis. Virtual visits may improve access to oculoplastic subspecialty care for patients from underserved areas.

Outcomes of Flap Amputation After Laser In Situ Keratomileusis.

PURPOSE: The aim of this study was to describe the indications and outcomes of flap amputation after laser in situ keratomileusis (LASIK) at a referral-based institution. METHODS: In this retrospective consecutive case series, medical records of patients who underwent LASIK flap amputation at Mayo Clinic, Rochester, MN, between January 1, 1998, and January 31, 2023, were reviewed. RESULTS: Fifteen eyes (15 patients) underwent flap amputation during the study period. The median age was 45 years (range, 25-71 years), and 8 patients (53%) were men. The median uncorrected visual acuity before flap amputation was 20/200 (range 20/40-hand motions). Indications for flap amputation included epithelial ingrowth (n = 6, 40%), infectious keratitis (n = 6, 40%), diffuse lamellar keratitis (n = 1, 7%), vegetative foreign body (n = 1, 7%), and astigmatism from fixed flap striae (n = 1, 7%). The median duration of follow-up was 8 months (range 1-234 months). Subsequent corneal interventions included chelation of calcific band keratopathy (n = 1, 7%), lamellar keratoplasty (n = 1, 7%), penetrating keratoplasty (n = 2, 18%), keratoprosthesis (n = 1, 7%), and rigid contact lens wear (n = 4, 27%). The final median best visual acuity was 20/25 (range 20/20-20/200). Compared with noninfectious indications for flap amputation, eyes with infectious indications had worse baseline median uncorrected visual acuity (hand motions vs. 20/63, P < 0.001), were more likely to undergo major corneal surgical intervention (50% vs. 11%), and had worse final median best visual acuity (20/50 vs. 20/20, P = 0.018). CONCLUSIONS: LASIK flap amputation is sometimes necessary to control threatening corneal diseases. Excellent visual outcomes were achieved in most cases, albeit with additional intervention or rigid contact lens wear.

Subretinal Phialophora Abscess in Chronic Granulomatous Disease.

PURPOSE: To report a rare case of a subretinal Phialophora richardsiae abscess in a patient with chronic granulomatous disease (CGD). METHODS: A 21-year-old male with CGD and a history of invasive pulmonary aspergillosis presented with progressive loss of vision and pain in his left eye. He was found to have a subretinal abscess with a macula involving serous retinal detachment. A diagnostic and therapeutic pars plana vitrectomy, subretinal biopsy with debridment, inferior retinectomy and silicone oil tamponade was performed. Intraoperative cultures grew Pleurostoma (Phialophora) richardsiae. He was treated with systemic liposomal amphotericin B and high-dose Posaconazole. However, eye eventually required enucleation. RESULTS: Preoperative visual acuity (VA) was light perception on the left eye and improved to count fingers at 4 weeks post-operative. However, VA rapidly declined to light perception, he developed an opaque white cataract, iris neovascularization, posterior synechiae, and corectopia. The retina remained attached under silicone oil. Histopathology revealed granuloma formation and active fungal elements. DISCUSSION/CONCLUSION: The case supports the importance of vitreoretinal surgery to determine a definitive systemic diagnosis. Treatment of Phialophora infection is surgically challenging to manage and has a poor visual prognosis in patients with CGD.

Ophthalmic adverse effects of BRAF inhibitors.

To determine the frequency, characteristics, and clinical course of ophthalmic side effects associated with systemic BRAF inhibitor therapy. Medical records of patients taking BRAF inhibitors for the treatment of systemic malignances at Mayo Clinic, Rochester from 01/01/2010 to 08/30/2021, were retrospectively reviewed. Of 901 patients, 14 (1.6%) patients experienced an ophthalmic side effect. Mean age at presentation of the side effect was 60 years (median 59, range 50-80) and 11 (79%) were male. The most common side effect was uveitis in 7 (50%) patients, followed by dry eye in 4 (29%) patients, and central serous chorioretinopathy in 2 (14%) patients, with singular cases of cranial nerve VI palsy and conjunctival edema. A comparison between individual BRAF inhibitors (vemurafenib vs. dabrafenib vs. encorafenib) revealed that patients taking encorafenib had a shorter interval to any ophthalmic adverse event (mean 55.6 vs. 9.8 vs. 4.0 months, p = 0.03) and were the only patients to experience documented dry eye syndrome (DES) in this series. Outcomes were known in 13 (93%) patients, and ophthalmic adverse effects resolved or were controlled without discontinuing therapy in 10 (77%). Uveitis was successfully treated with topical corticosteroids in 4 patients, while 3 patients with refractory uveitis (2 with panuveitis and 1 with unspecified uveitis) required discontinuation of BRAF inhibitor therapy. Ophthalmic adverse events related to systemic BRAF inhibitor use are rare, with estimated frequency of 1.6%. Most events can be treated with local ophthalmic therapy. BRAF inhibitors provide life-saving therapy, and their discontinuation should be avoided.

Population-based Rate and Patterns of Diplopia in Giant Cell Arteritis.

Giant cell arteritis (GCA) is the most common vasculitis in older adults with permanent vision loss as a feared complication. Diplopia has been reported in a small percentage of patients with visual manifestations. The goal of this study was to determine the population-based rates and patterns of binocular diplopia from GCA. The Rochester Epidemiology Project (REP), a medical records linkage system was used to identify all residents of Olmsted County, Minnesota, USA, diagnosed with GCA between January 1, 1950 and December 31, 2019. Medical records were then reviewed to identify patients with binocular diplopia from GCA. There were 301 incident cases of GCA from 1950 to 2019. Fourteen (5%) patients presented with binocular diplopia. Of these 14 patients, nine (3%) had constant diplopia and five (2%) had transient diplopia. Among patients with constant diplopia, cranial nerve VI involvement was suspected in four (44%) cases. Systemic symptoms and inflammatory markers were similar in patients with and without diplopia. There was no difference in the rate of anterior ischaemic optic neuropathy between the two groups (7% vs. 7%, p = 1.00). In conclusion, this population-based study showed that binocular diplopia was present in 5% of patients with GCA, which could either be transient or constant. GCA patients with diplopia had similar systemic manifestations and risk of vision loss as GCA patients without diplopia.

Clinical characteristics and outcomes of ocular adnexal mantle cell lymphoma.

PURPOSE: To compare characteristics of initial ocular adnexal (OA) mantle cell lymphoma (MCL) and initial systemic MCL. METHODS: Retrospective, comparative case series. Patients treated for MCL at Mayo Clinic from 1/1/1990 to 11/30/2020. MCL was classified as initial OA if first site was OA or initial systemic if first site was elsewhere with progression or recurrence to the OA region. OUTCOME MEASURES: Features, treatment, and survival. RESULTS: There were 50 patients with MCL, 23 initial OA and 27 initial systemic. Patients with initial OA MCL had more conjunctival (52% vs. 19%, p = .017) involvement and less frequently received chemotherapy plus autologous stem cell transplant (ASCT) (9% vs. 33%, p = .046) as initial treatment. Complete remission was achieved in 41 (91% vs. 74%, p = .152) patients. Five-year disease-specific survival was similar in initial OA and initial systemic MCL (92% vs. 83%, p = .187). Subanalysis of patients with initial OA MCL revealed 9 (39%) patients developed tumor recurrence, with mean time to recurrence of 28 months. Comparison (no recurrence vs. recurrence) of initial OA MCL patients revealed those with no recurrence had shorter mean final follow-up (3.3 vs. 9.8 years, p = .005) and more frequent initial treatment with rituximab-based chemotherapy plus ASCT (43% vs. 0%, p = .048). Recurrence had no effect on the 5-year age-adjusted risk of death from lymphoma (HR 2.17, 95% CI 0.55-9.09, p = .266). CONCLUSIONS: Initial OA and initial systemic MCL patients differ in presentation and management but have similar survival.

Anterior segment ischemia after laser for retinopathy of prematurity previously treated with antivascular endothelial growth factor.

PURPOSE: To assess the risk of vision-threatening anterior segment ischemia (ASI) among retinopathy of prematurity (ROP) patients treated with anti-VEGF followed by laser photocoagulation. METHODS: The medical records of all infants treated for threshold ROP with laser photocoagulation with and without prior anti-VEGF injections from January 1, 2002, through December 2018 at Mayo Clinic were retrospectively reviewed for the prevalence of vision-threatening ASI. RESULTS: A total of 241 eyes of 122 infants were included. Mean gestational age was 25.1 weeks (range, 22.9-28.7); mean birth weight was 687.6 g (range, 360-1310 g). Of the 54 eyes (27 patients) treated with anti-VEGF prior to laser, 4 developed ASI (including corneal edema, cataracts, and choroidal effusion) compared with 2 of the 187 eyes (95 patients) treated with laser therapy alone (P = 0.008). Infants receiving both anti-VEGF and laser had a younger gestational age at birth (24.5 vs 25.3 weeks; P < 0.001) and lower birth weight (591.4 g vs 715.0 g; P < 0.001) than those who received laser alone. In multivariate analysis, early gestational age at birth was associated with development of ASI (P = 0.03); the association with anti-VEGF treatment (P = 0.07) fell short of statistical significance. CONCLUSIONS: The prevalence of vision-threatening ASI was higher among infants treated with intravitreal anti-VEGF followed by laser compared to those treated with laser alone. Further investigation is warranted to confirm this finding and identify potential factors for decreasing the risk of ASI.

External validation of a nomogram predicting risk of bleeding control interventions after high-grade renal trauma: The Multi-institutional Genito-Urinary Trauma Study.

BACKGROUND: Renal trauma grading has a limited ability to distinguish patients who will need intervention after high-grade renal trauma (HGRT). A nomogram incorporating both clinical and radiologic factors has been previously developed to predict bleeding control interventions after HGRT. We aimed to externally validate this nomogram using multicenter data from level 1 trauma centers. METHODS: We gathered data from seven level 1 trauma centers. Patients with available initial computed tomography (CT) scans were included. Each CT scan was reviewed by two radiologists blinded to the intervention data. Nomogram variables included trauma mechanism, hypotension/shock, concomitant injuries, vascular contrast extravasation (VCE), pararenal hematoma extension, and hematoma rim distance (HRD). Mixed-effect logistic regression was used to assess the associations between the predictors and bleeding intervention. The prediction accuracy of the nomogram was assessed using the area under the receiver operating characteristic curve and its 95% confidence interval (CI). RESULTS: Overall, 569 HGRT patients were included for external validation. Injury mechanism was blunt in 89%. Using initial CT scans, 14% had VCE and median HRD was 1.7 (0.9-2.6) cm. Overall, 12% underwent bleeding control interventions including 34 angioembolizations and 24 nephrectomies. In the multivariable analysis, presence of VCE was associated with a threefold increase in the odds of bleeding interventions (odds ratio, 3.06; 95% CI, 1.44-6.50). Every centimeter increase in HRD was associated with 66% increase in odds of bleeding interventions. External validation of the model provided excellent discrimination in predicting bleeding interventions with an area under the curve of 0.88 (95% CI, 0.84-0.92). CONCLUSION: Our results reinforce the importance of radiologic findings such as VCE and hematoma characteristics in predicting bleeding control interventions after renal trauma. The prediction accuracy of the proposed nomogram remains high using external data. These variables can help to better risk stratify high-grade renal injuries. LEVEL OF EVIDENCE: Prognostic and epidemiological study, level III.

The American Association for the Surgery of Trauma Renal Grading System-Should Segmental Kidney Infarction be Classified as a Grade IV Injury?

PURPOSE: In 2018 the American Association for the Surgery of Trauma revised renal injury grading. One change was inclusion of segmental kidney infarction under grade IV injuries. We aimed to assess how segmental kidney infarction will change the scope of grade IV injuries and compare bleeding control interventions in those with and without isolated segmental kidney infarction. METHODS: We used high grade renal trauma data from 7 level 1 trauma centers from 2013 to 2018 as part of the Multi-institutional Genito-Urinary Trauma Study. Initial computerized tomography scans were reviewed to regrade the injuries. Injuries were categorized as isolated segmental kidney infarction if segmental parenchymal infarction was the only reason for inclusion under grade IV injury. All other grade IV injuries (including combined injury patterns) were categorized as without isolated segmental kidney infarction. Bleeding interventions were compared between those with and without isolated segmental kidney infarction. RESULTS: From 550 patients with high grade renal trauma and available computerized tomography, 250 (45%) were grade IV according to the 2018 American Association for the Surgery of Trauma grading system. Of these, 121 (48%) had isolated segmental kidney infarction. The majority of patients with isolated segmental kidney infarction (88%) would have been assigned a lower grade using the original 1989 grading system. Rate of bleeding control interventions was lower in isolated segmental kidney infarction compared to other grade IV injuries (7% vs 21%, p=0.002). Downgrading all patients with isolated segmental kidney infarction to grade III did not change the grading system's associations with bleeding interventions. CONCLUSIONS: Approximately half of the 2018 American Association for the Surgery of Trauma grade IV injuries have isolated segmental kidney infarction. Including isolated segmental kidney infarction in grade IV injuries increases the heterogeneity of these injuries without increasing the grading system's ability to predict bleeding interventions. In future iterations of the American Association for the Surgery of Trauma renal trauma grading isolated segmental kidney infarction could be reclassified as grade III injury.

Microorganisms and Antibiogram Patterns in Fournier's Gangrene: Contemporary Experience from a Single Tertiary Care Center.

PURPOSE: We evaluate the prevalent microorganisms, antibiotic sensitivity patterns and associated outcomes in patients with Fournier's gangrene. MATERIALS AND METHODS: A retrospective chart review of patients with Fournier's gangrene was conducted between October 2011 and April 2018 at our institution. Univariate analysis was performed using the independent t-test or Kruskal-Wallis H test for continuous variables and exact test for categorical variables. RESULTS: Of the 143 patients included in this study, wound culture was available in 131 (92%) patients with a median number of 3 microorganisms per wound. The most commonly grown pathogens were Staphylococcus species (66, 46%), Streptococcus species (53, 37%), Bacteroides species (34, 24%), Candida species (31, 22%), Escherichia coli (28, 20%) and Prevotella species (26, 18%). Most bacteria were sensitive to ampicillin-sulbactam, ceftriaxone, piperacillin-tazobactam, amikacin and cefepime, and resistant to ampicillin, trimethoprim-sulfamethoxazole, levofloxacin and clindamycin. Enterococcus faecalis and Streptococcus anginosus were resistant to vancomycin. The overall Fournier's gangrene mortality count was 14 (10%) patients. No association was noted between the type of infection and Fournier's gangrene severity index, length of hospital stay or mortality. CONCLUSIONS: At our institution Candida is a prevalent pathogen in the wound culture of patients with Fournier's gangrene. The resistance patterns for clindamycin and vancomycin are concerning. Addition of an antifungal agent to the empiric treatment should be considered based on clinical presentation.

Current Management of Extraperitoneal Bladder Injuries: Results from the Multi-Institutional Genito-Urinary Trauma Study (MiGUTS).

PURPOSE: We studied the current management trends for extraperitoneal bladder injuries and evaluated the use of operative repair versus catheter drainage, and the associated complications with each approach. MATERIALS AND METHODS: We prospectively collected data on bladder trauma from 20 level 1 trauma centers across the United States from 2013 to 2018. We excluded patients with intraperitoneal bladder injury and those who died within 24 hours of hospital arrival. We separated patients with extraperitoneal bladder injuries into 2 groups (catheter drainage vs operative repair) based on their initial management within the first 4 days and compared the rates of bladder injury related complications among them. Regression analyses were used to identify potential predictors of complications. RESULTS: From 323 bladder injuries we included 157 patients with extraperitoneal bladder injuries. Concomitant injuries occurred in 139 (88%) patients with pelvic fracture seen in 79%. Sixty-seven patients (43%) initially underwent operative repair for their extraperitoneal bladder injuries. The 3 most common reasons for operative repair were severity of injury or bladder neck injury (40%), injury found during laparotomy (39%) and concern for pelvic hardware contamination (28%). Significant complications were identified in 23% and 19% of the catheter drainage and operative repair groups, respectively (p=0.55). The only statistically significant predictor for complications was bladder neck or urethral injury (RR 2.69, 95% 1.21-5.97, p=0.01). CONCLUSIONS: In this large multi-institutional cohort, 43% of patients underwent surgical repair for initial management of extraperitoneal bladder injuries. We found no significant difference in complications between the initial management strategies of catheter drainage and operative repair. The most significant predictor for complications was concomitant urethral or bladder neck injury.

DNA methylation and FoxO3a regulate PHLPP1 expression in chondrocytes.

The protein phosphatase Phlpp1 is an essential enzyme for proper chondrocyte function. Altered Phlpp1 levels are associated with cancer and degenerative diseases such as osteoarthritis. While much is known about the post-transcriptional mechanisms controlling Phlpp1 levels, transcriptional regulation of the Phlpp1 gene locus is underexplored. We previously showed that CpG methylation of the PHLPP1 promoter is lower in osteoarthritic cartilage than in normal cartilage, and indirectly correlates with gene expression. Here we further defined the effects of DNA methylation on PHLPP1 promoter activity in chondrocytes. We cloned a 1791 bp fragment of the PHLPP1 promoter (-1589:+202) and found that the first 500 bp were required for maximal promoter activity. General methylation of CpG sites within this fragment significantly blunts transcriptional activity, whereas site-specific methyltransferases HhaI or HpaII decrease transcriptional activation by approximately 50%. We located putative FoxO consensus sites within the PHLPP1 promoter region. Inhibition of DNA methylation by incorporation of 5-azacytidine increases Phlpp1 mRNA levels, but FoxO inhibition abolishes this induction. To determine which FoxO transcription factor mediates Phlpp1 expression, we performed overexpression and siRNA-mediated knock down experiments. Overexpression of FoxO3a, but not FoxO1, increases Phlpp1 levels. Likewise, siRNAs targeting FoxO3a, but not FoxO1, diminished Phlpp1 levels. Last, FoxO inhibition increases glycosaminoglycan staining of cultured chondrocytes and leads to concomitant increases in FGF18 and HAS2 expression. Together, these data demonstrate that CpG methylation and FoxO3a regulate PHLPP1 expression.