Outcomes of a Modified Treatment Ladder Algorithm Using Retrobulbar Amphotericin B for Invasive Fungal Rhino-Orbital Sinusitis.

PURPOSE: To assess whether a modified treatment ladder algorithm incorporating transcutaneous retrobulbar amphotericin B (TRAMB) for invasive fungal rhino-orbital sinusitis can reduce the risk of exenteration without compromising survival. DESIGN: Retrospective, comparative clinical study with historical control subjects. METHODS: Fifty consecutive patients with biopsy-proven invasive fungal sinusitis and radiographic evidence of orbital involvement were evaluated at a single tertiary institution from 1999-2020. TRAMB was incorporated as part of the treatment algorithm in 2015. Demographics, underlying immune derangement, infective organism, ophthalmic examination, surgical care, and survival were compared in a quasiexperimental pre-post format, dividing patients into a pre-2015 group and a post-2015 group. Risk of exenteration and mortality were the primary outcomes. RESULTS: Baseline characteristics did not differ significantly between the 2 groups. Nearly all patients underwent a surgical intervention, most commonly functional endoscopic sinus surgery with debridement. TRAMB was administered to 72.7% of the post-2015 group. Exenteration was more common in the pre-2015 group (36.4% vs 9.1% [95% confidence interval {CI} 5.2-48.8]; P = .014), while mortality was similar (40.0% vs 36.7% [95% CI -22.1 to 29.3]; P = .816). After adjusting for potential confounders, patients treated after 2015 were found to have lower risk of exenteration (relative risk 0.28 [95% CI 0.08-0.99]; P = .049) and similar risk of mortality (relative risk 1.04 [95% CI 0.50-2.16]; P = .919). CONCLUSION: Compared with historical control subjects, patients with invasive fungal rhino-orbital sinusitis who were treated with a modified treatment ladder algorithm incorporating TRAMB had a lower risk of disfiguring exenteration without an apparent increase in the risk of mortality.

Quality-of-Life Outcomes for Excision and Reconstruction of Periocular Nonmelanoma Skin Cancer.

Background: Understanding how periocular nonmelanoma skin cancer (NMSC) impacts quality of life (QoL) provides insight into the patient experience. Objective: To prospectively measure QoL of individuals with surgically treated periocular NMSC. Methods: Responses to the skin cancer index (SCI) and FACE-Q questionnaires were obtained at preoperative (PRE), postoperative week 1 (POW1), and postoperative month 3 (POM3) visits. Statistical analysis was performed using paired t-test and stepwise linear regression. Results: Forty-five patients participated in the study. Improved QoL as reflected in an increased mean difference of the total SCI score at PRE and POM3 visits (25.8, 95% confidence interval [CI 20.0 to 31.6]) and FACE-Q early life impact of treatment score at POW1 and POM3 visits (19.0, 95% CI [14.9 to 23.0), and a decreased mean difference of the FACE-Q adverse effects score at POW1 and POM3 visits (-1.3, 95% CI [-2.4 to -0.1]) was observed. Linear regression of the SCI and FACE-Q scores using demographic and clinical attributes revealed several predictors of postoperative QoL. Conclusions: Surgical management of periocular NMSC results in improved QoL, demonstrated at the final postoperative visit.

Keratoplasty Outcomes in Patients With Uveitis.

PURPOSE: To examine the corneal transplant failure rates and associations with uveitic eye disease. METHODS: The retrospective chart review identified 70 eyes from 42 patients with uveitis that underwent 40 primary transplants and 30 repeat transplants at 2 major academic centers over a 9-year period. The graft failure rate was calculated. Variables hypothesized to be associated with graft failure were analyzed as covariates using a Cox proportional hazards analysis clustered by the patients to determine their association with failure rates. RESULTS: Of the 70 grafts, the mean duration of follow-up for patients was 40.6 months (range 4-90 months) and the median survival time was 24.1 months (interquartile range of 9-290 months). Twenty-two patients (52%) had graft failure. There was a higher rate of graft failure in patients with infectious uveitis as compared to those with noninfectious uveitis (hazard ratio 2.46, P = 0.031). Patients with successful grafts had their inflammation controlled for a longer period of time before transplantation as compared to those with failed grafts (38.6 vs. 13.6 months, P = 0.004). Worse preoperative visual acuities were significantly associated with graft failure (P < 0.001). CONCLUSIONS: There is limited knowledge of corneal transplant outcomes in uveitic patients in the current literature. In our study, over half of the grafts failed. Infectious uveitis (especially viral) was a strong predictor of graft failure. A shorter period of inflammation control before transplantation, previously failed grafts, and worse preoperative visual acuity were also associated with graft failure.

Corneal Light Scatter After Ultrathin Descemet Stripping Automated Endothelial Keratoplasty Versus Descemet Membrane Endothelial Keratoplasty in Descemet Endothelial Thickness Comparison Trial: A Randomized Controlled Trial.

PURPOSE: To compare the degree of corneal light scatter as measured by densitometry in ultrathin Descemet Stripping Automated Endothelial Keratoplasty (UT-DSAEK) and Descemet Membrane Endothelial Keratoplasty (DMEK) in the Descemet endothelial thickness comparison trial. METHODS: This was a prespecified secondary analysis of the Descemet endothelial thickness comparison trial, which was a prospective, randomized controlled trial. Subjects with isolated endothelial dysfunction were enrolled and were randomized to either UT-DSAEK or DMEK. Corneal opacity was quantitatively measured by Pentacam densitometry (OCULUS) at 3, 6, and 12 months. RESULTS: Fifty eyes of 38 patients were enrolled at the Casey Eye Institute at Oregon Health & Science University and the Byers Eye Institute at Stanford University. Corneal densitometry for the anterior and posterior layers improved in both UT-DSAEK and DMEK after surgery. The decrease was more pronounced in the posterior layer for both groups. However, there was no difference in the degree of corneal light scatter between UT-DSAEK and DMEK at postoperative month 12, and no difference in change in densitometry was observed between the 2 arms from baseline to month 12. CONCLUSIONS: Both UT-DSAEK and DMEK experience an improvement in the degree of corneal light scatter after surgery. However, there was no difference in densitometry between the 2 groups at month 12. Therefore, other factors such as higher order aberrations in the posterior cornea rather than stromal-stromal interface haze mediate the superior visual outcomes in DMEK compared with UT-DSAEK.

Descemet Stripping Only for a Chronic Descemet Detachment After Cataract Surgery.

PURPOSE: To describe a case of postsurgical corneal decompensation in a patient with Fuchs endothelial dystrophy with a sectoral Descemet detachment and corneal edema that was successfully managed with a targeted Descemet stripping only (DSO) procedure. METHODS: This is a case report and review of the literature. RESULTS: A female patient with Fuchs endothelial dystrophy presented with a 6-month history of a persistent sectoral Descemet membrane detachment after cataract surgery with overlying corneal edema. Specular microscopy demonstrated moderate cell dropout with a cell density of 929 cells/mm in the affected eye. Intracameral air injection was attempted without improvement, and a sectoral DSO procedure was performed. Netarsudil and prednisolone were used postoperatively, and she demonstrated gradual improvement with resolution of the edema by postoperative week 10 and a central endothelial cell density of 675 cells/mm by postoperative month 8. CONCLUSIONS: DSO is a viable therapy in certain cases of postsurgical corneal decompensation.

Prospective, randomized, eye-to-eye comparison of a new silicone corneal shield versus conventional bandage contact lens after photorefractive keratectomy.

PURPOSE: To compare uncorrected distance visual acuity (UDVA) and patient-reported outcomes with a new silicone corneal shield and a conventional bandage contact lens (BCL) after photorefractive keratectomy (PRK). SETTING: Stanford Eye Laser Center (Palo Alto, California) and Slade & Baker Vision (Houston, Texas). DESIGN: Prospective randomized cohort study. METHODS: Standardized bilateral wavefront-guided or wavefront-optimized PRK was performed in 25 patients with myopia. Each patient's dominant eye was randomized to either a silicone corneal shield or a conventional BCL, which was placed at the conclusion of surgery. The contralateral eye was assigned the other intervention. The UDVA and patient-reported outcomes were measured preoperatively, 1 hour after surgery, and at 1, 2, 3, 4, and 7 days postoperatively. RESULTS: At 1 day postoperatively, the mean logarithm of the minimum angle of resolution (logMAR) UDVA was 0.04 ± 0.16 (SD) in the silicone corneal shield group and 0.29 ± 0.22 in the BCL group (P < 0.01). At 7 days postoperatively, the mean logMAR UDVA was 0.09 ± 0.17 in the silicone corneal shield group and 0.23 ± 0.24 in the BCL group (P = .01). At 1 day through 3 days postoperatively, the patients reported greater pain, discomfort, foreign body sensation, and heavy eyelid in the eye with the silicone corneal shield. There was no statistically significant difference in the survey outcomes between the two groups at 4 days and 7 days postoperatively. CONCLUSIONS: The new silicone corneal shield was safe and effective, with faster visual recovery and a trend toward quicker epithelialization; however, it might be less comfortable than a conventional BCL.

Oral miltefosine for refractory Acanthamoeba keratitis.

PURPOSE: To report the first case of Acanthamoeba keratitis treated with oral miltefosine in the United States. OBSERVATIONS: A 17-year-old female with a history of orthokeratology contact lens wear presented after five months of left eye pain, redness, and photophobia. She was previously treated with antivirals and topical corticosteroids for presumed herpetic disease. She was found to have a large central ring infiltrate and corneal cultures were positive for Acanthamoeba. The infection progressed despite hourly PHMB 0.02% and chlorhexidine 0.02%, and oral vorizonazole. The patient was started on oral miltefosine 50 mg 3 times per day. Following one week of treatment, repeat cultures were positive for Acanthamoeba and therefore, the concentration of chlorhexidine was increased from 0.02% to 0.06% and PHMB was changed to propamidine isetionate (Brolene 0.1%). There was definite clinical improvement after five weeks of treatment with oral miltefosine, topical chlorhexidine 0.06% and propamidine isetionate 0.1%. CONCLUSIONS AND IMPORTANCE: Acanthamoeba keratitis is a challenging entity to treat and often associated with a poor prognosis. Oral miltefosine may offer additional therapeutic benefit in cases of refractory Acanthamoeba keratitis.

Hydrogel sealant to prevent recurrent epithelial ingrowth in the setting of a LASIK flap buttonhole.

PURPOSE: To report the first case of hydrogel sealant to prevent the recurrence of epithelial ingrowth in a LASIK flap buttonhole. OBSERVATIONS: A 67-year-old female presented ten years after undergoing bilateral LASIK with diffuse lamellar keratitis and flap dislodgement after blunt trauma to the right eye. She was found to have epithelial ingrowth with diffuse debris and striae, so her flap was lifted and the epithelial ingrowth was removed. However, a central buttonhole was noted intraoperatively. Once all the epithelium was removed, the flap was repositioned and hydrogel sealant (ReSure, Ocular Therapeutix, Bedford, MA) was used to fill the buttonhole as well as seal down the edges of the flap. Sixteen months postoperatively, the patient's uncorrected visual acuity was 20/50-2 and there was no recurrence of the epithelial ingrowth at the edges of the buttonhole. CONCLUSIONS AND IMPORTANCE: Preventing the recurrence of epithelial ingrowth is a challenging situation, especially in the setting of a LASIK flap buttonhole. The use of hydrogel sealant in the buttonhole and around the edges of the flap may offer an elegant and effective solution.

Invasive Fungal Sinusitis: Risk Factors for Visual Acuity Outcomes and Mortality.

PURPOSE: Invasive fungal sinusitis is a rare but potentially lethal disease that primarily affects immunocompromised patients. The purpose of this study was to review an academic medical center's experience in the presentation, diagnosis, and treatment of invasive fungal sinusitis. METHODS: A retrospective chart review was performed at a single institution over a 17-year period. Medical records, radiographic imaging, and operative reports were analyzed. Bivariate and multivariable analyses were performed to determine factors that affected visual acuity outcomes and mortality. RESULTS: Fifty-five patients with histopathologically confirmed invasive fungal sinusitis were included. The average duration of follow up was 1.8 ± 2.6 years (range: 1 week to 10 years). The most common causes of immunosuppression were hematologic malignancy (45%), diabetes (31%), and organ transplantation (9%). At presentation, 35% of individuals were neutropenic (absolute neutrophil count < 500/µl). All patients received systemic antifungal treatment. A surgical intervention was performed on 50 patients (91%), and all but one had functional endoscopic sinus surgery. Nine (16%) patients underwent orbital exenteration. Multivariable analysis of visual acuity outcomes demonstrated that individuals infected with Zygomycota had 6-7 lines worse vision than those infected with Ascomycota (mean difference in logMAR 0.66, 95% confidence interval 0.27 to 1.06, p = 0.001). Patients who had functional endoscopic sinus surgery had 7-8 lines better visual acuity than those without functional endoscopic sinus surgery (mean difference in logMAR -0.76, 95% confidence interval -1.13 to -0.38, p < 0.001). The overall death rate due to infection was 24%. Bivariate models demonstrated no difference in mortality in patients receiving exenteration versus those who did not (p = 0.14). Multivariable analysis of mortality demonstrated that neutropenia increased mortality (adjusted odds ratio 10.05, 95% confidence interval 1.49 to 67.67, p = 0.02). Having a greater number of surgeries was associated with an increased rate of survival (adjusted odds ratio 0.39, 95% confidence interval 0.15 to 0.96, p = 0.04). CONCLUSIONS: Invasive fungal sinusitis is an aggressive disease with significant mortality. Patients with neutropenia had a lower rate of survival, and infection with Zygomycota was associated with worse visual acuity outcomes. Those having functional endoscopic sinus surgery had better final visual acuity, and an increased number of surgeries was associated with a decreased chance of death. Exenteration yielded no observed survival benefit.Endoscopic sinus debridement portends better visual acuity outcomes in patients with invasive fungal sinusitis, whereas exenteration yields no difference in survival benefit.

Congenital sodium diarrhea and chorioretinal coloboma with optic disc coloboma in a patient with biallelic SPINT2 mutations, including p.(Tyr163Cys).

Congenital sodium diarrhea is a rare and life-threatening disorder characterized by a severe, secretory diarrhea containing high concentrations of sodium, leading to hyponatremia and metabolic acidosis. It may occur in isolation or in association with systemic features such as facial dysmorphism, choanal atresia, imperforate anus, and corneal erosions. Mutations in the serine protease inhibitor, Kunitz-Type 2 (SPINT2) gene have been associated with congenital sodium diarrhea and additional syndromic features. We present a child with congenital sodium diarrhea, cleft lip and palate, corneal erosions, optic nerve coloboma, and intermittent exotropia who was found to have biallelic mutations in SPINT2. One mutation, c.488A > G, predicting p.(Tyr163Cys), has been previously associated with a syndromic form of congenital sodium diarrhea. The other mutation, c.166_167dupTA, predicting p.(Asn57Thrfs*24) has not previously been reported and is likely a novel pathogenic variant for this disorder. We found only one other report of an optic nerve coloboma associated with SPINT2 mutations and this occurred in a patient with congenital tufting enteropathy. Our patient confirms an association of ocular coloboma with presumed loss of SPINT2 function.

Diagnosing Distensible Venous Malformations of the Orbit With Diffusion-weighted Magnetic Resonance Imaging.

PURPOSE: To compare the diffusion-weighted imaging of nonthrombosed distensible venous malformations of the orbit with that of other histologically-proven orbital tumors. DESIGN: Retrospective case-control study. METHODS: Patients with nonthrombosed distensible venous malformations of the orbit and patients with other histologically-proven orbital tumors were selected for chart review. The main outcome measure was the apparent diffusion coefficient of these lesions. RESULTS: Sixty-seven patients qualified for chart review; 9 patients had nonthrombosed distensible venous malformations and 58 patients had other histologically-proven tumors. Three of the 9 patients with nonthrombosed distensible venous malformations were initially misdiagnosed as having had solid orbital tumors. The mean apparent diffusion coefficient of distensible venous malformations was 2.80 ± 0.48 × 10-3 mm2/s, whereas the mean apparent diffusion coefficient of other histologically-proven tumors was 1.18 ± 0.39 × 10-3 mm2/s (P < .001). The mean apparent diffusion coefficient ranged from 2.42 to 3.94 × 10-3 mm2/s in the distensible venous malformation group, whereas other histologically-proven tumors ranged from 0.53 to 2.08 × 10-3 mm2/s. Therefore, in this single-institution series, a threshold value of 2.10 × 10-3 mm2/s was 100% sensitive and 100% specific for distensible venous malformations. CONCLUSION: Certain nonthrombosed distensible venous malformations can evade diagnostic suspicion and mimic solid orbital tumors on standard magnetic resonance imaging sequences. In this single-institution series, diffusion-weighted imaging effectively distinguished these nonthrombosed distensible venous malformations from other orbital tumors.

Normalization of Congenital Venous Stasis Retinopathy Following Sclerotherapy of a Macrocystic Lymphatic Malformation.

The authors describe, for the first time to their knowledge, a case of a congenital macrocystic lymphatic malformation of the orbit with associated venous stasis retinopathy that acutely normalized after drainage and sclerotherapy of the lesion. Prenatal ultrasound revealed prominence of the left orbital soft tissue, and at birth, the patient was noted to have unilateral proptosis, tortuous retinal vessels, and intraretinal hemorrhages in all 4 quadrants in the left eye. MRI demonstrated a primarily intraconal, multiloculated, T2-hyperintense mass consistent with a lymphatic malformation. Ultrasound-guided cyst aspiration and sclerotherapy was performed, with subsequent improvement of the proptosis and resolution of the vessel tortuosity and intraretinal hemorrhages. Although venous stasis retinopathy is usually related to central retinal vein occlusion or carotid artery occlusive disease, any entity that increases orbital venous resistance can generate retinal venous dilation and intraretinal hemorrhages, including an orbital lymphatic malformation.

Invasive fungal sinusitis: treatment of the orbit.

PURPOSE OF REVIEW: To summarize diagnostic techniques for invasive fungal rhinosinusitis and provide a review of treatment options once disease has spread to the orbit. RECENT FINDINGS: Improved imaging criteria, polymerase chain reaction and other serologic tests show promise in advancing our ability to accurately diagnose invasive fungal disease. Currently, there exists three treatment options for infected orbital tissue: exenteration, conservative debridement and transcutaneous retrobulbar injection of amphotericin B. Exenteration, the most frequently reported intervention, has not been proven to enhance survival. Conservative debridement and transcutaneous retrobulbar injection of amphotericin B are increasingly considered reasonable first-line options. SUMMARY: Although investigative tools are improving, invasive fungal rhinosinusitis can still pose a diagnostic challenge. No one treatment option for the orbit has been proven superior to another. Therefore, it is justified to initiate therapy by prioritizing less morbid procedures. If deterioration is continually noted, more invasive interventions can then be employed. The treatment algorithm established at our institution is provided.

Retrobulbar Injection of Amphotericin B for Orbital Mucormycosis.

A 68-year-old immunocompromised man with rhino-orbital-cerebral mucormycosis was treated with retrobulbar injections of amphotericin B deoxycholate in conjunction with intravenous antifungals and endoscopic sinus debridement. Transient episodes of orbital inflammation were noted after retrobulbar injections, but progression of orbital infection was halted and visual acuity restored with eventual hospital discharge. To the authors' knowledge, clearance of orbital mucormycosis with retrobulbar amphotericin B injections has not been previously reported. This intervention may be a viable therapeutic option in cases of orbital mucormycosis where aggressive orbital debridement is not favored and/or the burden of orbital disease is not substantial. However, physicians should be aware of the risk of transient orbital inflammation secondary to retrobulbar amphotericin B deoxycholate.

Orbital compartment syndrome following retrobulbar injection of amphotericin B for invasive fungal disease.

PURPOSE: To describe a complication of retrobulbar amphotericin B injections in the treatment of invasive rhino-orbital asperigillosis. OBSERVATIONS: 27 year-old renal transplant recipient presented with a two-week history of headache, binocular diplopia and proptosis of the left eye. Endonasal biopsy on hospital day 3 confirmed the diagnosis of rhino-orbital invasive Aspergillus fumigatus involving the left orbital apex.In addition to systemic antifungal treatment and cessation of immunosuppression, retrobulbar amphotericin B injections (3.5 mg/1 ml) combined with endoscopic local debridement were initiated when the patient developed progressive visual loss. Retrobulbar injections were administered on hospital days 8, 10, 14, 17, and 20. Endoscopic debridement occurred on hospital days 10 and 16.After the fifth retrobulbar amphotericin B injection, the patient developed acute orbital compartment syndrome with intraocular pressures ranging from 47 to 86 mmHg and vision declined to 20/200, requiring emergent lateral canthotomy and superior and inferior cantholysis. Close observation without further intervention resulted in return of vision to 20/20 and normalization of intraocular pressure. CONCLUSION AND IMPORTANCE: Retrobulbar amphotericin B in combination with local debridement may be considered an alternative to exenteration for invasive aspergillosis secondary to reversible immunosuppression. To the authors' knowledge, orbital compartment syndrome secondary to retrobulbar amphotericin B administration has not previously been reported. Patients should be counseled on the risk of severe local inflammation due to amphotericin B. More research is needed to establish the most appropriate dosing, frequency, and duration of retrobulbar amphotericin B injections in the treatment of life-threatening Aspergillus infections.

Midface-lift with lateral orbicularis oculi flap excision or imbrication.

BACKGROUND: The orbicularis oculi advancement midface-lift treats rhytides and infraorbital grooves. The muscle flap smoothes the subciliary lid and cheek zone but may produce contour abnormalities laterally. OBJECTIVE: To describe a technique of orbicularis flap midface-lift with excision or imbrication of muscle and to evaluate the results--to include characterizing the lateral contour abnormalities--in a large series. MATERIALS AND METHODS: A total of 108 patients received a primary aesthetic orbicularis advancement flap midface-lift. Two masked observers scored each patient's result based on preoperative and postoperative images. Patients also scored their satisfaction of the results of their procedures. Patient age, sex, surgical technique specifics (i.e., excision or imbrication), and complications were recorded. RESULTS: All patients had favorable aesthetic improvement scores with no significant complications. In patients who received orbicularis excision (N = 33), lateral hollowing occurred in 3 patients; none desired correction. With an imbrication technique (N = 75), lateral mounding occurred in 6 patients; 3 of these patients were treated with elliptical excision. CONCLUSION: Orbicularis advancement midface-lifting was safe and effective in rejuvenating the midface in this series. Aesthetic complications were infrequent but include lateral hollowing when orbicularis is excised and lateral mounding with muscle imbrication.

Bilateral dacryocystoceles in a pregnant woman.

The authors describe, for the first time, bilateral, sequential large dacryocystoceles during pregnancy and review the literature for this presentation. A 26-year-old, 15-week pregnant woman presented with OD epiphora, diplopia, and pain in the setting of an inferomedial orbital mass. Surgical exploration and histopathology were consistent with a dacryocystocele, and a dacryocystorhinostomy was curative. She returned at 34-week gestation, with an identical presentation on the left side. Review of the literature reveals that dacryocystoceles occasionally present in adults; however, bilateral involvement may be unusual. Bilateral dacryocystoceles have not been previously reported in a pregnant woman.