Multispecialty Management of Metastatic Colon Adenocarcinoma Involving the Extraocular Muscles: Primary Excision and Simultaneous Treatment of Strabismus With a Review of the Literature.

Metastatic colon adenocarcinoma involving the extraocular muscles is extremely rare. It usually develops following the diagnosis of the systemic disease and therefore, management and treatment require a multispecialty approach. Within this manuscript, we provide a summary of cases of orbital metastasis secondary to colon cancer. We further discuss a detailed case of a 42-year-old male patient who developed recent-onset diplopia in the left gaze. Orbital CT imaging showed a localized, well-circumscribed enlargement of the right medial rectus muscle. The biopsy of the right medial rectus showed adenocarcinoma originating from the gastrointestinal system. Further workup revealed colon adenocarcinoma with multiple metastatic sites. The patient started systemic chemotherapy. After 2 months of chemotherapy (5-fluouracil, oxaliplatin, irinotecan, and leucovorin), all systemic metastatic sites regressed; however, his medial rectus muscle continued to grow, causing compressive optic neuropathy. The patient underwent excisional biopsy of the right medial rectus muscle with simultaneous repair of the strabismus with transposition of superior and inferior recti muscles. He continued with systemic chemotherapy. Follow up in 1 year revealed no local orbital tumor recurrence with excellent visual acuity and no diplopia in primary gaze.

Resolution of cyclic esotropia with 5-year follow-up after brief Fresnel prism treatment.

Cyclic esotropia is a rare form of strabismus that is characterized by a recurring esotropic deviation, usually with a 48-hour cycle. On esotropic days, the patient has a constant deviation with suppression, followed by a day with straight eyes and good binocular function. We report a case of cyclic esotropia in which the cycling resolved with 2 months of Fresnel prism for the amount of the distance deviation on her "straight" days. Five years later, with low plus hyperopic correction, she remains with a stable esophoria and normal stereopsis.

Comparison of Unilateral and Bilateral Surgical Approaches for the Treatment of Age-Related Divergence Insufficiency Esotropia.

PURPOSE: Age-related divergence insufficiency-esotropia (ARDIE) is characterized by greater esodeviation at distance than near. This study aims to compare the outcomes of unilateral and bilateral surgical approaches. PATIENTS AND METHODS: Sixty-two cases treated at the Kellogg Eye Center, the University of Michigan, from 1995 to 2018 were retrospectively reviewed. One surgeon used unilateral procedures including unilateral medial rectus recession (n = 24, group 1) or unilateral recession-resection (n = 18, group 2) with an adjustable suture. Another surgeon used bilateral medial rectus recession with fixed sutures (n = 20, group 3). RESULTS: For patients with distance esodeviation <15∆, postoperative distance deviations in both group 1 and group 3 were not statistically different (p = .352). For patients with esodeviations 15-20∆, postoperative distance deviations in all 3 groups were also not statistically different (p = .142). Similarly, patients with deviations >20∆ did not show significantly different postoperative distance alignment (p = .082) between group 2 and 3. Overall, group 2 had the highest overall success rate (90%) (mean at distance = 1.17∆ exodeviation, at near = 2.33∆ exodeviation). CONCLUSION: Both unilateral medial rectus recession ± lateral rectus resection and bilateral medial rectus recession surgical approaches produced similar favorable outcomes in ARDIE.

A 2020 Update on 20/20 X 2: Diplopia after Ocular Surgery: Diplopia after Orbital Surgery.

In a review of 261 strabismus surgeries performed after previous orbital surgery, it was found that diplopia associated with orbital surgery most commonly occurs after orbital decompression for thyroid eye disease or after repair of orbital fractures. Other types of orbital surgery account for only a small number of cases. While the orbital surgery itself may contribute to the development or worsening of diplopia, in most cases, the post-operative strabismus is largely attributable to the underlying disease or trauma. However, in a small number of cases, a specific surgical misadventure can result in diplopia.

Novel TMEM98, MFRP, PRSS56 variants in a large United States high hyperopia and nanophthalmos cohort.

Nanophthalmos is a rare condition defined by a small, structurally normal eye with resultant high hyperopia. While six genes have been implicated in this hereditary condition (MFRP, PRSS56, MYRF, TMEM98, CRB1,VMD2/BEST1), the relative contribution of these to nanophthalmos or to less severe high hyperopia (≥ + 5.50 spherical equivalent) has not been fully elucidated. We collected probands and families (n = 56) with high hyperopia or nanophthalmos (≤ 21.0 mm axial length). Of 53 families that passed quality control, plausible genetic diagnoses were identified in 10/53 (18.8%) by high-throughput panel or pooled exome sequencing. These include 1 TMEM98 family (1.9%), 5 MFRP families (9.4%), and 4 PRSS56 families (7.5%), with 4 additional families having single allelic hits in MFRP or PRSS56 (7.5%). A novel deleterious TMEM98 variant (NM_015544.3, c.602G>C, p.(Arg201Pro)) segregated with disease in 4 affected members of a family. Multiple novel missense and frameshift variants in MFRP and PRSS56 were identified. PRSS56 families were more likely to have choroidal folds than other solved families, while MFRP families were more likely to have retinal degeneration. Together, this study defines the prevalence of nanophthalmos gene variants in high hyperopia and nanophthalmos and indicates that a large fraction of cases remain outside of single gene coding sequences.

Age at Craniosynostosis Surgery and Its Impact on Ophthalmologic Diagnoses: A Single-Center Retrospective Review.

BACKGROUND: Ocular abnormalities in craniosynostosis are a persistent concern for patients and providers, and some surgeons feel that early surgical intervention for synostosis alleviates the progression of ophthalmologic abnormalities. In contradistinction, the authors hypothesize that operating early will have no bearing on postoperative ophthalmologic outcomes. METHODS: Single-suture craniosynostosis patients who underwent surgical correction between 1989 and 2015 were reviewed. Patients with multisuture craniosynostosis, syndromic diagnoses, no preoperative ophthalmology evaluation, and less than 2 years of follow-up were excluded. Logistic regression was used to determine odds of preoperative and postoperative ophthalmologic abnormalities by age, while controlling for patient-level covariates. RESULTS: One hundred seventy-two patients met inclusion criteria. The median age at surgery was 10 months (interquartile range, 7 to 12.9 months). Increasing age at the time of surgery was associated with increased odds of preoperative ophthalmologic diagnoses (OR, 1.06; p = 0.037) but not postoperative diagnoses (OR, 1.00; p = 0.91). Increasing age at surgery was also not associated with increased odds of ophthalmologic diagnoses, regardless of timing (OR, 1.04; p = 0.08). Patients with coronal synostosis (OR, 3.94; p = 0.036) had significantly higher odds of preoperative ophthalmologic diagnoses. Patients with metopic (OR, 5.60; p < 0.001) and coronal (OR, 7.13; p < 0.001) synostosis had significantly higher odds of postoperative ophthalmologic diagnoses. CONCLUSIONS: After reviewing an expansive cohort, associations of both overall and postoperative ophthalmologic diagnoses with age at surgery were not found. The authors' findings thus run counter to the theory that early surgical intervention lessens the likelihood of postoperative ophthalmologic diagnoses and improves ophthalmologic outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Variants in myelin regulatory factor (MYRF) cause autosomal dominant and syndromic nanophthalmos in humans and retinal degeneration in mice.

Nanophthalmos is a rare, potentially devastating eye condition characterized by small eyes with relatively normal anatomy, a high hyperopic refractive error, and frequent association with angle closure glaucoma and vision loss. The condition constitutes the extreme of hyperopia or farsightedness, a common refractive error that is associated with strabismus and amblyopia in children. NNO1 was the first mapped nanophthalmos locus. We used combined pooled exome sequencing and strong linkage data in the large family used to map this locus to identify a canonical splice site alteration upstream of the last exon of the gene encoding myelin regulatory factor (MYRF c.3376-1G>A), a membrane bound transcription factor that undergoes autoproteolytic cleavage for nuclear localization. This variant produced a stable RNA transcript, leading to a frameshift mutation p.Gly1126Valfs*31 in the C-terminus of the protein. In addition, we identified an early truncating MYRF frameshift mutation, c.769dupC (p.S264QfsX74), in a patient with extreme axial hyperopia and syndromic features. Myrf conditional knockout mice (CKO) developed depigmentation of the retinal pigment epithelium (RPE) and retinal degeneration supporting a role of this gene in retinal and RPE development. Furthermore, we demonstrated the reduced expression of Tmem98, another known nanophthalmos gene, in Myrf CKO mice, and the physical interaction of MYRF with TMEM98. Our study establishes MYRF as a nanophthalmos gene and uncovers a new pathway for eye growth and development.

Surgical Management of Ophthalmoplegia.

Surgical management-depending upon the severity of the ophthalmoplegia-ranges from restorative to palliative. In paresis with reasonable residual muscle function and ductions, the goal of the surgery is not only to restore single vision in primary position but also to provide a relatively normal field of single binocular vision. With complete paralysis of a single muscle or more than one muscle served by a single cranial nerve (third), in addition to conventional recess or resect surgery, the transposition of still-functioning muscles is often needed to obtain a durable result and restore at least some field of single binocular vision. In complete ophthalmoplegia, the benefits of the surgery are limited; but even in these cases, surgery can often reduce the need for an awkward head posture and improve appearance.

The effect of oral statin therapy on strabismus in patients with thyroid eye disease.

BACKGROUND: Statins, known to possess anti-inflammatory characteristics, have recently been identified as potentially reducing the risk of developing thyroid eye disease (TED) in Graves disease patients. The current study investigates the effect of oral statin therapy on strabismus related to TED. METHODS: This is a retrospective review of patients with a diagnosis of both TED and restrictive strabismus. Oral statin users and nonusers were analyzed for smoking status, previous radioactive iodine, thyroidectomy, number of decompressions, motility restriction, amount of strabismus, number of surgeries, surgical dose, and number of muscles involved on radiography. RESULTS: Thirty patients (average age, 63.9 years; 50% male; 59% current/former smokers) were included: 12 statin users and 18 nonusers. Statin users averaged fewer decompressions (1.3 in users vs 2.4 in nonusers [P = 0.04]). Statin users on average had 15 mm of total strabismus surgery compared with 21.4 mm in the nonuser group (P = 0.09) and had fewer muscles involved radiographically (4.3 vs 5.1 [P = 0.08]) CONCLUSIONS: Compared to nonusers, statin users tended to have fewer decompressions, less restriction, fewer surgeries, and fewer muscles involved despite having more current smokers (36% vs 5%), more males, more RAI, and fewer thyroidectomies, all of which are associated with worse TED. In our cohort of patients with TED and strabismus, statin therapy significantly reduced the number of orbital decompressions. Oral statin therapy also trended toward reducing the number and amount of strabismus surgeries as well as radiographic indication of muscle involvement, although these did not meet statistical significance.

Why strabismus surgery works: the legend of the dose-response curve.

BACKGROUND: The dose-response relationship has historically been regarded as an important approach to improve the success of strabismus surgery. The purpose of this study was to explore the role of preoperative deviation, in addition to the amount of surgery, as a predictor of the response to strabismus surgery. METHODS: Dose-response data from a variety of sources are analyzed in a multiple linear regression model with both preoperative deviation and surgical dose as independent variables. P values and partial correlations from these regressions are used to investigate the relative contribution of each factor. RESULTS: These analyses consistently show that preoperative deviation is statistically a better predictor of the response to surgery than the amount of surgery. In data sets where one factor is constant, preoperative deviation alone accounts for 78%, and the amount of surgery alone accounts for 46% of the variance of the surgical response. CONCLUSIONS: The importance of preoperative deviation as an independent variable implies a biologic response to strabismus surgery that tends to produce more change in alignment when the deviation is large and less when it is small. The strong association of amount of surgery with surgical outcome in bivariate analysis studies may be an artifact of making the amount of surgery a strict function of the preoperative deviation. Because of its lesser role as a predictor, accuracy of preoperative deviation measurement upon which the amount of surgery is based, refinement of the dose-response curve, or use of adjustable sutures may have less potential to improve surgical outcome than generally believed.

The Necessity of Amblyopia.

A general property of nervous system development is that correlated activity is used to organize topographic projections. This correlated activity is typically produced by electrical coupling of adjacent neurons; however, electrical coupling is not possible for retinal ganglion cells in separate eyes that need to be precisely mapped to the same place in the brain. This forces the visual system to rely on environmental stimuli to produce the correlated activity that drives the development of binocularity, with amblyopia as necessary consequence when visual experience is abnormal. The characteristic visual deficits in both the amblyopic and the sound eyes can be understood in the context of these normal developmental processes. The auditory system provides another example-where precise connections between paired sense organs must rely on environmental stimuli for normal development-in which the analogous condition of amblyaudia occurs.

Partial tendon recession for small-angle vertical strabismus.

PURPOSE: To evaluate the effectiveness of the partial tendon recession procedure in correcting small-angle vertical deviations. METHODS: The medical records of patients who underwent partial tendon recession (one pole) were reviewed retrospectively. Orthophoria was the primary outcome success criterion; residual deviation, torsion, and the dose-response relationship were also evaluated. A secondary analysis was performed on subsets of patients with thyroid eye disease (TED) and those with procedures on a muscle that had previous surgery. RESULTS: A total of 53 procedures in 44 patients (average age, 58 years; age range 8-88 years) were evaluated. The mean preoperative vertical deviation was 4.3Δ ± 1.8Δ (range, 2Δ-9Δ); the mean postoperative vertical deviation was 0Δ ± 2.3Δ. The mean response to surgery was 1.5Δ/mm. In the entire cohort, 62% of the procedures resulted in orthophoria, but 82% of patients had resolution of vertical diplopia with a single procedure. In TED patients, 60% of the procedures resulted in orthophoria, whereas only 29% of procedures on previously operated muscles resulted in orthophoria. CONCLUSIONS: Partial tendon recession of vertical rectus muscles reliably corrects small vertical deviations. This is equally true for patients with TED, but results are less predictable with reoperated muscles.

"Tag-Team" Orbital and Strabismus Surgeries with Immediate Reconstruction After Tumor Excision Metastatic to the Inferior Rectus.

Carcinoid tumors are rare, slow-growing, low-grade neuroendocrine tumors with a propensity for orbital metastatic spread. The typical treatment paradigm for localized orbital disease involves excision, adjuvant radiotherapy, and/or receptor-targeted chemotherapy, followed by delayed evaluation for reconstructive strabismus surgery. We present a 58-year-old female patient with carcinoid tumor metastatic to the right inferior rectus muscle who presented with worsening binocular diplopia. The patient underwent coordinated "tag-team" orbital and strabismus surgeries that included excision of the right inferior rectus muscle to the annulus of Zinn followed immediately by reconstructive strabismus surgery. The patient required 1 additional strabismus surgery 1 year later. Follow up revealed no tumor recurrence at 4 years, and excellent binocular vision with good function. Deep orbital and strabismus surgeries, when performed simultaneously in a "tag-team" approach, may offer superior functional outcomes and improved patient quality of life, with expedited functional recovery. This approach may become a new treatment paradigm for surgical disease processes localized to the extraocular muscles.

Small Deviations: Vertical, Horizontal, and Combined.

INTRODUCTION AND PURPOSE: Symptomatic, small-angle strabismus is largely an acquired problem of adults that has previously been managed with prism spectacles. This paper will explore surgical options that are becoming increasingly popular. METHODS: The special issues that confound surgical treatment of small-angle strabismus are considered. Surgical procedures described in the literature and in the author's experience that address these issues are reviewed. RESULTS: Several recently described surgical techniques show promise for treatment of small-angle strabismus in adults. Their use is illustrated in a case report. Review of the author's practice shows a rapid increase in surgery for small-angle strabismus. CONCLUSIONS: Surgical strategies for small deviations are increasingly important to meet the spectacle-free expectations of our adult patients.