Publications

PURPOSE: To compare outcomes of phacoemulsification and endocyclophotocoagulation with either dual blade goniotomy (PEcK) or two trabecular stents (ICE2). SETTING: Retrospective, nonrandomized comparative study from a level 3 triage center. METHODS: One hundred and seventy charts and a total of 1294 visits were reviewed following either PEcK or ICE2 from 2018 to 2022. One hundred and twenty-eight patients had PEcK and 42 underwent ICE2. Patients with less than 30 days of follow-up were excluded. The mean follow-up time was 505 ± 308 days. Two Kaplan-Meier curves (KM) assessed survival with ≤ baseline medications while maintaining (1) [GIC - Goal IOP Criteria] IOP ≤ goal IOP or (2) [PRC - Percent Reduction Criteria] IOP reduction ≥ 20% with 5 mmHg ≤ IOP ≤ 21 mmHg for at least two consecutive visits. IOP and medication burden reduction were compared using a paired t-test. RESULTS: Most patients were Caucasian (65%) and had mild-stage glaucoma (43%). The most common glaucoma type was primary open-angle glaucoma (58%). Average age was 72.2 years at the time of surgery. Mean preoperative IOP was 17.58 ± 4.98 mmHg on 3.00 ± 1.41 medications in PEcK and 15.36 ± 3.58 mmHg on 1.81 ± 1.11 medications in ICE2 (p = 0.015 for IOP; p < 0.001 for medications). Under GIC, the success rate was significantly higher in PEcK at POM6 (69% vs 46%, p < 0.001) and POY1 (63% vs 36%, p < 0.001). Under PRC, the success rate was significantly higher in PEcK at POM6 (73% vs 61%, p = 0.031) and POY1 (67% vs 50%, p = 0.028). Mean reductions at POY1 were 5.00 ± 4.31 mmHg on 1.35 ± 1.08 less medications after PEcK and 3.14 ± 2.83 mmHg on 1.01 ± 0.94 less medications after ICE2 (p < 0.001 at POY1 for IOP; p < 0.05 after POW6 for medications). CONCLUSION: Both PEcK and ICE2 reduce medication and IOP from baseline, with PEcK having more favorable GIC and PRC success rates and greater IOP and medication reduction at 1 year.

BACKGROUND: Orbital cavernous hemangiomas (OCH) are the most common adult orbital tumor and represent an ideal index lesion for endonasal orbital tumor surgery. In order to standardize outcomes reporting, an anatomic-based staging system was developed. METHODS: An international, multidisciplinary panel of 23 experts in orbital tumor surgery was formed. A modified Delphi method was used to develop the cavernous hemangioma exclusively endonasal resection (CHEER) staging system with a total of 2 rounds being completed. RESULTS: Tumors medial to a plane along the long axis of the optic nerve may be considered amenable for an exclusively endonasal resection. In select cases, tumors may extend inferolaterally if the tumor remains below a plane from the contralateral naris through the long axis of the optic nerve (ie, plane of resectability [POR]). This definition reached consensus with 91.3% of panelists in agreement. Five stages were designed based on increasing technical resection difficulty and potential for morbidity. Stages were based on the relationship of the tumor to the extraocular muscles, the inferomedial muscular trunk of the ophthalmic artery (IMT), and orbital foramina. Staging by anatomic location also reached consensus with 87.0% of panelists in agreement. Size was not included in the staging system due to the lack of agreement on the contribution of size to resection difficulty. CONCLUSION: Endoscopic orbital tumor surgery is a nascent field with a growing, yet heterogeneous, body of literature. The CHEER staging system is designed to facilitate international, high-quality, standardized studies establishing the safety, efficacy, and outcomes of endonasal resection of OCH.

The lacrimal gland undergoes significant structural and functional deterioration with aging. Marked with increased inflammation and fibrosis, the aged lacrimal gland is unable to perform its protective function. As a result, the ocular surface becomes highly susceptible to various ocular surface pathologies, including corneal epitheliopathy. We and others have previously shown that mast cells mediate tissue inflammation by recruiting other immune cells. However, despite their well-known characteristics of secreting various inflammatory mediators, whether mast cells contribute to the immune cell aggregation and activation, and acinar dystrophy of the aged lacrimal gland has not been investigated. Here, we demonstrate the role of mast cells in age-related lacrimal gland pathophysiology using mast cell-deficient (cKitw-sh) mice. Our data demonstrated a significant increase in mast cell frequencies and immune cell infiltration in the lacrimal gland of aged mice. Interestingly, mast cell deficiency resulted in a substantial reduction in inflammation and preservation of lacrimal gland structure, suggesting that mast cells mediate the aging process of the lacrimal gland.

Keratitis induced by bacterial toxins, including lipopolysaccharide (LPS), is a major cause of corneal opacity and vision loss. Our previous study demonstrates hepatocyte growth factor (HGF) promotes epithelial wound healing following mechanical corneal injury. Here, we investigated whether HGF has the capacity to suppress infectious inflammatory corneal opacity using a new model of LPS-induced keratitis. Keratitis, induced by two intrastromal injections of LPS on day 1 and 4 in C57BL/6 mice, resulted in significant corneal opacity for up to day 10. Following keratitis induction, corneas were topically treated with 0.1% HGF or PBS thrice daily for 5 days. HGF-treated mice showed a significantly smaller area of corneal opacity compared to PBS-treated mice, thus improving corneal transparency. Moreover, HGF treatment resulted in suppression of α-SMA expression, compared to PBS treatment. HGF-treated corneas showed normalized corneal structure and reduced expression of pro-inflammatory cytokine, demonstrating that HGF restores corneal architecture and immune quiescence in corneas with LPS-induced keratitis. These findings offer novel insight into the potential application of HGF-based therapies for the prevention and treatment of infection-induced corneal opacity.

PURPOSE: To evaluate the efficacy and safety of cenegermin 0.002% ophthalmic drops in the management of pediatric neurotrophic keratopathy (NK). METHODS: Retrospective chart review of children under the age of 18 years diagnosed with NK at Boston Children's Hospital/Massachusetts Eye and Ear Infirmary and treated with topical cenegermin 0.002% ophthalmic solution between June 2018 and June 2021 was performed. Data collection included etiology of NK, age at time of initiation of topical cenegermin, laterality, ethnicity, gender, history of previous ocular therapy, pre- and post-therapy best corrected visual acuity, pre- and post-therapy cornea examination, any adverse events from topical cenegermin, associated ocular conditions, and history of ocular surgeries. RESULTS: The current study includes four eyes of four pediatric patients with a mean age of 4.5 ± 2.0 years at the time of initiation of topical cenegermin therapy. The mean time from NK diagnosis until start of topical cenegermin drops was 5.2 ± 4.3 months and mean follow-up time was 15 ± 9.6 months. In all four patients, marked improvement in epitheliopathy was demonstrated after completion of therapy. Best corrected visual acuity was measurable in 3 eyes of 3 patients, and it improved from a mean of 0.07 ± 0.01 to a mean of 0.29 ± 0.26 (P = 0.3). No adverse events related to cenegermin therapy were noted. CONCLUSION: Topical cenegermin was effective in improving corneal healing for pediatric NK.

PURPOSE: To evaluate the outcomes of inferior oblique (IO) weakening surgery, whether recession or myectomy, and to assess the dose-response relationship and correlation with angle of preoperative hypertropia. METHODS: The medical records of all patients with vertical deviation in primary gaze who underwent unilateral IO-weakening surgery, either recession or myectomy, at Boston Children's Hospital over an 8-year period with a minimum postoperative follow-up of 1 month were reviewed retrospectively. Outcome measures were effect of IO weakening surgery on vertical deviation in primary gaze and its correlation with the preoperative angle of hyperdeviation. Secondary outcomes included resolution of abnormal head posture, reduction of ocular torsion, and postoperative under- and overcorrection RESULTS: A total of 94 patients were identified (mean age at surgery, 29.3 ± 19.8 years; range, 1-69). The mean postoperative follow-up period was 17.2 ± 15 months. IO recession was performed in 30 patients; IO myectomy, in 64. Surgical success in primary position was achieved in 72 patients (77%), with resolution of anomalous preoperative head posture in 93%. The mean effect on alignment in primary position was 11.3 ± 6.8. The response to IO-weakening surgery was strongly correlated with the preoperative hyperdeviation for both recession (R = 0.53) and myectomy (R = 0.87). CONCLUSIONS: As with other types of strabismus surgery, IO weakening has a "self-grading" contribution, in which the surgical effect strongly correlates with the magnitude of preoperative deviation. A large range of vertical misalignment can be corrected with the same surgical approach.

PURPOSE: Angle surgery is the gold standard for the management of many types of childhood glaucoma, yet glaucoma drainage devices (GDD) are effective tools for refractory advanced cases or secondary childhood glaucomas. The purpose of this article is to review recently published literature focused on the use of GDDs for pediatric glaucoma, including GDD general principles and surgical outcomes. METHODS: Literature review of various electronic databases was performed. RESULTS: 71 papers were reviewed for outcomes of GDD in childhood glaucomas. Success rates were usually defined by intraocular pressure (IOP) of 5-22 mmHg, with or without medications. Success rates were typically higher for non-valved GDDs but varied by length of follow-up. Non-valved GDDs afford lower and longer-lasting IOP control in pediatric eyes than valved GDD, however, no randomized controlled trials exist in childhood glaucoma. CONCLUSION: Various designs of GDDs are available for management of childhood glaucoma with good short-term success rates; individual patient factors should be taken into consideration when selecting a specific device.

PURPOSE: To report a case of 16-month-old boy with a novel variant TSPAN12 gene-presenting as unilateral myopia, pediatric cataract, and heterochromia in a patient with familial exudative vitreoretinopathy. OBSERVATION: A 16-month-old otherwise healthy boy was referred to Boston Children's Hospital for evaluation of strabismus. Ocular examination revealed intermittent esotropia, left hypotropia, and limited left eye elevation in both adduction and abduction. Full cycloplegic hyperopic correction of +3.50 diopters (D) over both eyes was given to the patient. Over several months, refraction of the right eye showed progressive myopia (-6.00 D) with new onset iris heterochromia. Fundus examination showed there was a large area of chorioretinal atrophy with abrupt ending of the blood vessels; anterior to the ora serrata there were diffuse vitreous bands and veils that reached the lens anteriorly in direct contact with the lenticular opacity. A novel heterozygous nonsense likely pathogenic variant was identified in the TSPAN12 gene (NM_012338.3) c.315T>A (p.Cys105Ter) confirming the diagnosis of FEVR. CONCLUSION AND IMPORTANCE: Asymmetric FEVR rarely present with unilateral axial myopia however association with acquired heterochromia and cataract has never been reported. We report a case of FEVR caused by a novel TSPAN12 likely pathogenic nonsense variant presenting as unilateral progressive myopia, acquired heterochromia, and pediatric cataract.

PURPOSE: The aim of this study was to evaluate the clinical and topographic features of posterior polymorphous corneal dystrophy (PPCD) in children aged 15 years or younger with a long-term follow-up. Retrospective case series. METHODS: A retrospective chart review of patients who were diagnosed with PPCD at Boston Children's Hospital from 1999 to 2020 was performed. Data collected included age at the time of diagnosis, slit lamp findings, cycloplegic refraction, best-corrected visual acuity, central corneal thickness, specular microscopy, and corneal topography findings whenever available. RESULTS: Twenty-seven eyes of 19 patients were included (11 unilateral and 8 bilateral cases). Ten patients were girls (52.6%). Left eye was affected in 14 eyes. The mean age at the time of diagnosis was 8.5 ± 3.3 years, with a mean follow-up of 5.3 years. In unilateral cases, there was a statistically significant difference in the endothelial cell density (P = 0.01), coefficient variation (P = 0.03), and hexagonality (P = 0.01) between the affected and the contralateral unaffected eyes. The mean best-corrected visual acuity at initial presentation was 0.8 ± 0.2 compared with 0.9 ± 0.08 in unaffected eyes (P = 0.04). The mean astigmatism was higher in the affected eye (+1.7 diopters) compared with (+1.00) the unaffected eye (P = 0.07). At initial presentation, 7 of 27 eyes had amblyopia, which resolved, either partially or completely, in 5 eyes after treatment. CONCLUSIONS: PPCD can present early in children with astigmatism and anisometropic amblyopia. A careful slit lamp examination for children presenting with anisoastigmatism is necessary to diagnose PPCD. Contrary to adults, presentation is often unilateral. Such patients should be followed up regularly with cycloplegic retinoscopy to prevent and treat refractive amblyopia if present.

PURPOSE OF REVIEW: We discuss the preoperative, intraoperative, and postoperative considerations for cataract surgery in eyes with high myopia. We also reviewed the recent literature on refractive outcomes and complications of cataract surgery in myopic eyes. RECENT FINDINGS: Several novel intraocular lens (IOL) power calculation formulas have recently been developed to optimize refractive outcomes. Haigis formula is the most accurate among the third-generation IOL formulas. Novel formulas such as Barrett Universal II, Kane, and modified Wang-Koch adjustment for Holladay I formula provide a better refractive prediction compared with old formulas. Intraoperatively, the chopping technique is preferred to minimize pressure on weak zonules and reduce the incidence of posterior capsule rupture. Anterior capsular polishing is recommended to reduce the risk of postoperative capsular contraction syndrome (CCS). Postoperatively, complications such as refractive surprises, intraocular pressure spikes, and CCS remain higher in myopic eyes. Only 63% of myopic patients with axial length more than 26 mm achieve a visual acuity at least 20/40 after cataract surgery, mainly because of coexisting ocular comorbidities. SUMMARY: There are multiple preoperative, intraoperative, and postoperative considerations when performing cataract surgery in myopic eyes. Further research is needed to optimize the refractive outcomes in these eyes and determine the best IOL formula. Surgeons should be adept and knowledgeable with different techniques to manage intraoperative complications.

OBJECTIVES: 1) To elucidate the role of collector channels in the aqueous humor outflow pathway 2) To suggest anatomic and functional methods of imaging collector channels in-vitro and in-vivo and 3) To discuss the role of such imaging modalities in the surgical management of glaucoma. METHODS: A thorough literature search was conducted on databases for studies published in English regarding the available methods to determine the role of collecting channels in normal and glaucomatous patients and to assess their patency. RESULTS: Intraocular pressure (IOP) exists as a balance between aqueous humor production and aqueous humor outflow. Collector channels are an essential anatomical constituent of the distal portion of the conventional aqueous humor outflow pathway. There are different surgical options for glaucoma management and with the recent advances in Schlemm's canal-based surgeries, collector channel's patency became a key factor in determining the optimum management for the glaucomatous eye. The advent of anatomic imaging methods has improved the ability to visualize collector channel morphology in-vitro, including swept-source optical coherence tomography (SS-OCT), spectral domain optical coherence tomography (SD-OCT), micro-computed tomography (micro CT), new immunohistochemistry techniques and scanning electron microscopy. The recent advent of real-time assessment of collector channel patency (including evaluation of episcleral venous outflow, observation of episcleral venous fluid wave, and tracer studies utilizing fluorescein, indocyanine green, and trypan blue) has been validated by the aforementioned anatomic imaging modalities. CONCLUSIONS: New modalities of in-vitro and in-vivo studies of collector channels provide promise to aid in the assessment of collector channel patency and individualization of surgical management for glaucoma patients.

PURPOSE: The Paul glaucoma implant (PGI, Advanced Ophthalmic Innovations, Singapore, Republic of Singapore) is a recently developed novel non-valved glaucoma drainage device (GDD) designed to effectively reduce the intraocular pressure (IOP) in glaucoma patients with a theoretically reduced risk of postoperative complications such as hypotony, endothelial cell loss, strabismus, and diplopia. Limited literature has evaluated its use in adult glaucoma; however, its use in pediatric glaucoma has not been reported to date. We present our early experience with PGI in refractory childhood glaucoma. PATIENTS AND METHODS: This study was retrospective single-surgeon case series in a single tertiary center. RESULTS: Three eyes of 3 patients with childhood glaucoma were enrolled in the study. During nine months of follow-up, postoperative IOP and number of glaucoma medications were significantly lower than preoperative values in all the enrolled patients. None of the patients developed postoperative complications including postoperative hypotony, choroidal detachment, endophthalmitis, or corneal decompensation. CONCLUSION: PGI is an efficient and relatively safe surgical treatment option in patients with refractory childhood glaucoma. Further studies with larger number of participants and longer follow-up period are required to confirm our encouraging results.

PRCIS: The effectiveness of Ahmed glaucoma valve (AGV) and Baerveldt glaucoma implant (BGI) was comparable in the management of childhood glaucoma over the long term despite initial better success rate with BGI. There were higher tube block and retraction rates in the BGI group and higher tube exposure rates in the AGV group. PURPOSE: To evaluate the outcomes and safety of AGV and BGI in childhood glaucoma. MATERIALS AND METHODS: We performed a systematic literature review of publications from 1990 to 2022 in PubMed, EMBASE, ClinicalTrials.gov, Ovid MEDLINE, Cochrane CENTRAL, and google scholar for studies evaluating AGV and BGI in childhood glaucoma. Primary outcome measures were intraocular pressure (IOP) reduction and glaucoma medication reduction. The secondary outcome measures were the success rates and incidence of postoperative complications. We conducted a meta-analysis using a random effects model. RESULTS: Thirty-two studies met the inclusion criteria. A total of 1480 eyes were included. The mean IOP reduction was 15.08 mm Hg ( P < 0.00001) for AGV and 14.62 ( P < 0.00001) for the BGI group. The mean difference between pre and postoperative glaucoma medications was 1 ( P < 0.00001) fewer medications in the AGV group and 0.95 ( P < 0.0001) fewer medications in the BGI group. There was a lower success rate in the AGV versus BGI groups at 2 years [63% vs 83%, respectively ( P < 0.0001) and 3 years (43% vs 79%, respectively ( P < 0.0001)]; however, the success was higher for AGV at 5 years (63% vs 56% in the BGI group, P < 0.001). The incidence of postoperative complications was comparable in the AGV and BGI groups, with rates of 28% and 27%, respectively. CONCLUSIONS: The IOP and glaucoma medication reduction, success rates, and incidence of postoperative complications were comparable in Ahmed and Baerveldt groups. Most literature comes from retrospective low-quality studies on refractory childhood glaucoma. Further larger cohort studies are needed.