Progressive Necrotizing Ocular Surface Disease, Despite Immunosuppression.

A 60-year-old man was referred with 2 years of left conjunctivitis that persisted despite antibiotic and systemic corticosteroid therapy. The severity and extent of surface disease had increased slowly after prior dacryocystorhinostomy. Subsequent conjunctival biopsies demonstrated granulomas with patchy necrosis but no evidence of malignancy or organisms; systemic screening for sarcoidosis and tuberculosis was negative. A markedly thickened and inflamed left ocular surface was present on referral, with areas of conjunctival ischemia and patchy white slough on the tarsi. Further ocular surface biopsy did not reveal malignancy, and therefore mycobacterial infection was considered a possible cause. Mycobacterium tuberculosis was cultured, albeit only after repeated conjunctival swabs and biopsies. Appropriate treatment led to a very rapid resolution of ocular surface disease. Localized periocular tuberculosis is extremely rare outside developing nations, and its rarity may cause this differential diagnosis for persistent severe ocular surface disease to be overlooked in industrialized nations.

One-stage Intraconal Volume Modification for Exposed and Nonexposed Ball Implants.

PURPOSE: To assess long-term outcomes and reinterventions for exposed and nonexposed intraconal orbital implants after single-stage socket revisional surgery. METHODS: Retrospective case-note review of patients with exposed or nonexposed orbital ball implants, who underwent a single-stage ball exchange (Group I) or ball removal with dermis-fat graft (Group II); Group I was subdivided as having either exposed (A) or nonexposed (B) implants. Outcomes were compared with similar cohorts undergoing multistage surgery. RESULTS: Of 172 patients (54% male), 153 (89%) underwent ball exchange (Group I) and 19 (11%) had dermis-fat graft (Group II). With a mean follow up of 7.8 years, Group I patients without ball exposure (Group IB) had a slightly higher rate of reintervention for persistent volume deficit (21% vs. 9%; p = 0.163) and implant migration (6% vs. 0%; p = 0.091), while Group IA patients-having surgery for exposed implants-had more reexposures (7% vs. 3%; p = 0.270). Single-stage and 2-stage surgery had similar reintervention rates, with the exception of a trend toward fewer volume enhancements for those with nonexposed implants (17% vs. 30%; p = 0.380), and a shorter time to (re)exposure for exposed implants after 2-stage procedures (mean 0.33 vs. 3.5 years; p = 0.571). Group II patients required further volume enhancement in 32% of 1-stage procedures, and one patient needed graft removal. CONCLUSION: Single-stage volume modification is effective and the results are comparable to staged surgery for either exposed or nonexposed implants. Most patients report a stable prosthesis and satisfactory cosmesis, after a faster rehabilitation.

Long-Term Surgical Outcome for Orbital Solitary Fibrous Tumors.

PURPOSE: To report long-term outcomes after surgery for orbital solitary fibrous tumors. METHODS: Retrospective review of patients with orbital solitary fibrous tumor, first seen between 1971 and 2022. Primary excisions were grouped as (A) surgically intact, (B) macroscopic, but with cell spillage, or (C) known incomplete excision. RESULTS: Fifty-nine patients (31 female; 53%) presented at a mean age of 43.0 years (19-82 years), with 5 patients (8.5%) having malignant solitary fibrous tumors. Average follow up was 11.4 years (median 7.8; range 1-43 years). There were 28 of 59 (47%) group A patients with 1 of 28 (3%) having recurrence, 20 of 59 (34%) group B having 6 of 20 (30%) recurrences, and 11 of 59 (19%) group C with 9 of 11 (82%) recurrence ( p < 0.001 for recurrence rate). At a mean of 8.9 (range 1-23.6) years after initial treatment, continued local tumor growth was evident in 16 (27%) patients, with higher-grade recurrence in 3 of 14 (21%) cases. No patient had systemic disease at presentation, but 2 of 59 patients (3%) developed metastases at 22 and 30 years after first treatment. The 10-year progression-free survival was 94% (group A), 60% (group B), and 36% (group C). Tumor disruption or incomplete excision (groups B + C) carries the highest risk of tumor recurrence (hazard ratio 15.0; 95% confidence interval, 1.98-114; p = 0.009), with no correlation to tumor size or histology. CONCLUSIONS: Orbital solitary fibrous tumors have a low recurrence rate with surgically intact excision; piecemeal excision, capsular disruption, or known incomplete resection have a high recurrence rate, which can occur decades later. Baseline postoperative scans is recommended, together with long-term clinical and interval imaging.

Periocular Mass Due to Persistent Secretion Within a Transplanted Parotid Duct.

A male patient underwent microvascular transplantation of an autologous submandibular gland and its associated (Wharton's) duct for management of very severe right keratoconjunctivitis sicca due to Stevens-Johnson syndrome; due to hypersecretion, the gland was later removed in toto. Twenty-two years later, he presented with a nontender, sausage-like mass lying subcutaneously in the right temple. Intraoperatively a fluctuant tubular mass passing from the temporalis fossa to the superotemporal conjunctiva was identified and excised intact. Histology showed a slightly proteinaceous fluid within a duct lined with cuboidal epithelium, this being compatible with Wharton's duct. This case highlights that iatrogenic causes should be considered with any history of periocular injury or surgery.

Periosteal fixation of the medial and lateral recti for large-angle incomitant exotropia.

PURPOSE: To describe the evolution of a surgical technique for the correction of large-angle incomitant exodeviations. METHODS: Retrospective review of an interventional case series from 2005 to 2019 in a single centre, with analysis of surgical procedure, prism diopter (PD) deviations and complications. RESULTS: Thirty-one patients underwent surgery at an average age of 42 years (range 4-75 years) for minimal medial rectus function, mostly from oculomotor nerve palsy (23/31; 74%). The mean pre-operative exodeviation was 75 PD (range 30-200PD). Sixteen patients (52%) had undergone previous strabismus surgery. Thirty-eight operations were performed in which the medial rectus insertion was anchored to the periosteum of the posterior lacrimal crest via a retrocaruncular transconjunctival approach. The ipsilateral lateral rectus (LR) was disinserted and fixed to lateral orbital tissue in 29/38 (76%) operations, injected with botulinum toxin in 5, recessed in 2 and had already undergone maximal LR recession in 2. In all but the first 8 operations, temporary limbal sutures were passed through the eyelids to maximally adduct the globe post-operatively. At last follow-up (mean 24 months; range 2-130), the mean reduction in exodeviation was 49PD (range 10-80) and overall residual deviation was 26PD (range 80PD base-in to 14PD base-out). The 5 LR toxin procedures had a mean reduction of 22PD (range 10-40). Seven patients had persistent diplopia, one a transient corneal erosion and one caruncle suture exposure 4 years after surgery. CONCLUSION: Large-angle exodeviations can be markedly improved by bi-rectus fixation. This approach is both safe and effective and can be performed in complex patients with multiple previous procedures.

Extensive Sclerosis ("mummification") in Lacrimal Gland Pleomorphic Adenoma May Indicate Neighboring Malignant Transformation.

Salivary gland pleomorphic adenomas not uncommonly show extensive sclerosis ("dense hyalinization," "coagulative necrosis," or "mummification"), which arise spontaneously or after prior surgery, and this change is considered a high-risk factor for malignant transformation of benign salivary adenomas. While minor hyalinization is common in lacrimal gland adenomas, massive sclerosis-where almost all (90% or more) of the tumor is replaced by an amorphous hyaline material-is extremely rare. Four patients (2 males) are described in whom, despite not having an acute inflammatory episode, their lacrimal gland tumor showed marked sclerotic necrosis within the majority of either the benign or malignant parts of the tumor. Three tumors had evidence of malignant change, 2 to adenocarcinoma, and 1 to mucoepidermoid carcinoma, but none of the malignant areas showed perineural or endovascular invasion. Extensive sclerosis in association with a lacrimal gland pleomorphic adenoma (LGPA) is rare (4/110 of the cases) and-as with salivary adenomas-appears to be associated with a high chance of associated malignant change. Both the surgeon and the histopathologist should regard extensive sclerotic necrosis as a harbinger for malignant change in association with benign pleomorphic adenomas of the lacrimal gland.

Periocular Presentation of Solitary Plasmacytomas and Multiple Myeloma.

AIMS: To describe patients with periocular solitary extramedullary plasmacytoma (SEMP) and multiple myeloma (MM), together with an estimate of the risk of progression from SEMP to MM. PATIENTS AND METHODS: A retrospective case-note review for patients seen between 1978 and 2020, examining demographics, presentation, imaging, pathology, management, and outcome. RESULTS: Twenty patients (10 male; 50%) presented at a mean age of 60.9 years, with an average symptom duration of 4.5 months. Ten (50%) patients had known systemic myeloma at ophthalmic presentation (the MM group) and, on average, they presented one decade earlier than those with occult MM discovered after orbital biopsy (p = 0.06); the majority (9/15; 60%) of patients with MM were female, whereas there was a male bias (4/5; 80%) with SEMP (p = 0.30). Most tumors (15/20; 75%) were within the anterior part of the orbit, especially superolaterally (16 patients; 80%), and the soft-tissue mass often appeared to "explode" from the frontal bone or greater wing of the sphenoid (16/20; 80%). Full treatment details were known for 19 patients: 6 (32%) had solely orbital radiotherapy, 4 (21%) chemotherapy, 6 (32%) combined chemoradiation, and 3 (16%) had combined chemoradiation with stem-cell transplant (Table 3). After an average follow up of 58 months, 1/5 (20%) patients with SEMP and 11/15 (73%) with MM had tumor-related death. The overall survival probability for all 20 patients with periocular plasmacytoma was 34% at 5 and 10 years, with MM patients having a worse outlook (27% 5-year, and 18% 10-year survival) compared with SEMP (53% survival at 5 and 10 years) (p = 0.18). None of the 5 patients with SEMP progressed to systemic MM over an average follow up of 9.1 years. CONCLUSIONS: Although 50% patients with periocular plasmacytoma appear to have a SEMP at ophthalmic presentation, a half of these patients were found to have occult MM within 6 months of biopsy. Of those without systemic disease around the time of biopsy, none developed MM over an average follow up of more than 9 years.

Could Extension Into the Lacrimal Gland and Sac Thwart Topical Chemotherapy for Intraepithelial Sebaceous Carcinoma?

PURPOSE: To identify the frequency of intraepithelial (Pagetoid) spread beyond the ocular surface-namely beyond conjunctiva and cornea-in patients undergoing orbital exenteration for advanced periocular Sebaceous carcinoma (SC). DESIGN: A retrospective, noncomparative observational case series. SUBJECTS: Patients undergoing orbital exenteration for biopsy-proven SC, at Moorfields Eye Hospital between 1997 and 2013. METHODS: Review of clinical records and histological specimens, with particularly reference to involvement of conjunctiva and the extent of Pagetoid infiltration beyond the examinable ocular surface-here termed "hidden" disease. MAIN OUTCOME MEASURES: Histological evidence of intraepithelial SC within the lacrimal sac or lacrimal gland. RESULTS: Twenty-nine patients had clinical data and histological specimens adequate for review. Seventeen (59%) did not have a discrete mass (clinically or histologically) and, on clinical examination, were thought to only have extensive intraepithelial carcinoma; foci of microscopic invasion were, however, detected histologically in 11/17 (65%) of these specimens. Moreover, the in situ carcinoma was found to have invaded far in lacrimal gland ductules in 1/17 patients, in the lacrimal sac (in 2 patients; 12%) or in both the gland and sac (in 2 patients); these 5/17 (29%) cases all showed extensive poorly differentiated intraepithelial SC. Of the 12 other patients who had both Pagetoid spread and a clinically evident nodule, 3 had histological evidence of "hidden" disease. CONCLUSION: Although-due to their being operated in the era prior to the accepted usage of topical therapy for this condition-some of these exenterations might have had particularly advanced in situ SC, over a quarter of patients with periocular SC warranting orbital exenteration show "hidden" intraepithelial tumor within the lacrimal gland and sac. This important finding might significantly reduce the efficacy (particularly in the lacrimal gland) of the various topical therapies used for in situ SC of the ocular surface, and it also emphasizes the importance of excising both the lacrimal gland and sac in all orbital exenterations for this particular tumor.

Orbital involvement of Sitosterolemia.

Sitosterolemia is a rare inherited condition in which plant sterols are stored and deposited in the tissues. Described in 1974 by Battacharyya and Connor, it is characterized by tendon and tuberous xanthomas and a propensity to premature coronary atherosclerosis. We present the first reported case of the disease being manifest in the periorbital region. A 44-year-old man presented with a six-month history of swelling below the left eyebrow overlying the orbital rim, but without displacement of the globe. Magnetic resonance imaging identified a soft tissue mass within the orbit, with subsequent biopsy confirming a xanthogranulomatous process consistent with the diagnosis of sitosterolemia. Management of sitosterolemia aims to reduce plasma plant sterol concentrations which subsequently lowers serum cholesterol reducing the xanthomas and atherosclerotic cardiovascular diseases. This report highlights a rare, under-recognised condition (and indeed the first reporting periocular disease), and the potential dangers if misdiagnosed as hypercholesterolemia.

Extension of Masses Involving the Lacrimal Sac to Above the Medial Canthal Tendon.

PURPOSE: Retention mucoceles of the lacrimal sac almost always expand below the medial canthal tendon (MCT), whereas the very much rarer malignancies involving the lacrimal sac may progress to form a mass above the tendon. In this study, the incidence of malignancy was determined for patients with a preoperative decision to undergo biopsy for a clinically suspect, hard lacrimal sac mass, together with the proportion having a tumor extending above the MCT. METHODS: Patients thought-on the basis of having a firm, immobile mass centered on the lacrimal sac fossa-to possibly have lacrimal sac malignancy were identified from a database of biopsies between 1989 and 2020. A retrospective review of their clinical, radiologic, and pathologic records was undertaken. RESULTS: Fifty-three patients (24 male; 45%) underwent biopsy of atypical masses of the lacrimal sac, of which 47 of 53 (89%) extended above the MCT. Seventy-seven percent (41/53) patients had malignancy-26 primary carcinomas and 15 secondary tumors (14 lymphomas or hematopoietic and 1 neuroendocrine)-and 12 had benign conditions (6 transitional cell papillomatosis, 5 chronic inflammation, and 1 solitary fibrous tumor); all the benign pathologies extended above the MCT. The age at presentation and duration of symptoms was similar in patients with benign or malignant pathology. One-fifth of malignant lesions had pain, whereas all the benign conditions were painless, and acute dacryocystitis was relatively uncommon-occurring in only 13% of patients. CONCLUSIONS: If a firm and immobile lacrimal sac mass extends above the MCT, it has about a 74% chance of being malignant and, if pain is present, the lesion is more likely to be so. Clinically suspicious masses in the lacrimal sac fossa, whether benign or malignant, appear to present at the same age and with a similar duration of symptoms.

Rapid Rehabilitation With Skin-Muscle Sparing Orbital Exenteration: A Single-Center Series.

AIMS: To examine the features and clinical management of patients who underwent skin-muscle sparing orbital exenteration in a tertiary referral center. PATIENTS AND METHOD: Retrospective case-note review for patients undergoing skin-muscle sparing orbital exenteration at Moorfields Eye Hospital between 1997 and 2012. Patient demographics, clinical features, histopathology, clearance, surgery, adjuvant therapy, and outcomes were analyzed. RESULTS: Seventy-four patients (33 male; 45%) had skin-muscle sparing orbital exenteration at a median age of 63.8 years (median 65.5, range 13-96 years) for malignancies primarily arising in the eyelids (34 cases; 46%), orbit (25 cases; 34%) or conjunctiva (15 cases; 20%). The commonest pathologies were sebaceous carcinoma (20 cases; 27%), melanoma (19 cases; 26%), squamous cell carcinoma (12 cases; 16%), and basal cell carcinoma (9 cases; 12%). The patients had very rapid rehabilitation with primary closure of skin-muscle flaps over the cavity, either directly (63/74 patients; 85%), or with addition of local flaps. Local radiotherapy had been given before exenteration to 18 (24%) patients, was administered after exenteration in 19 (26%) patients, and both before and after surgery in 5 (7%); those having postoperative radiotherapy were referred at 2-3 weeks after exenteration, and the initial prosthetics fitting was started at 3-6 weeks after surgery. Thirty-eight (51%) patients died during a follow-up of 1-164 months (mean 55, median 47 months); 20/38 (53%) died from metastases-although 9/20 had known metastatic disease prior to palliative exenteration. Three patients were alive with apparently inactive metastases at 30, 39, and 140 months after surgery. CONCLUSION: Direct closure of skin-and-muscle flaps is achievable in almost all undergoing orbital exenteration. In contrast to skin-grafting, free myocutaneous flaps or secondary intention healing, this allows early referral if adjunctive orbital radiotherapy is needed, and the initial fitting of prosthetics can be within weeks of surgery. The technique also avoids the much greater donor-site morbidity of other reconstructive techniques, such as local or free myocutaneous flaps.

Day-Case Admission for External Dacryocystorhinostomy in Preschool Children.

PURPOSE: Epistaxis during or after dacryocystorhinostomy may present a risk of circulatory compromise, particularly in young children. In view of this concern, we reviewed the outcome and complications of external dacryocystorhinostomy in preschool children, aged less than 4½ years. DESIGN: Retrospective noncomparative series. PATIENTS AND METHODS: A case-note review for a series of preschool children undergoing external dacryocystorhinostomy as a day-case admission at Moorfields Eye Hospital between 1992 and 2018; all surgery was consultant-led. Details were taken of the type of surgery, any intraoperative or postoperative complications (surgical or anesthetic), any unplanned admissions after surgery, and the functional outcome. To assess the veracity of the medical records, the parents for a sample of 67 children were contacted to check whether there had been any unrecorded events or concerns. OUTCOME MEASURES: Anesthetic or surgical complications, unplanned admissions, and postoperative events. RESULTS: One-hundred and eighty-seven children (117 boys; 63%) underwent 228 external dacryocystorhinostomies during 201 admissions, the average admission age being 36.8 months (median, 37.5; range, 5.5-53.5 months). Forty-one children (20%) underwent bilateral dacryocystorhinostomy: the 27 having simultaneous bilateral surgery dacryocystorhinostomy were operated at a mean age of 38.2 months (median, 37.5; range, 15.5-53.5 months), this being significantly different from the average age at first operation in 14 children undergoing sequential admission for bilateral dacryocystorhinostomy (mean, 24.9 months; median, 27.0; range, 5.5-42.5) (p = 0.0023). No adverse anesthetic events were recorded, 2 children (2 dacryocystorhinostomies) required temporary nasal packing at the end of surgery for epistaxis, and one further child was admitted for overnight observation because of persistent mild epistaxis after bilateral dacryocystorhinostomy. Three children (3 dacryocystorhinostomies) had a mild, self-limiting secondary epistaxis, and there were no unplanned emergency admissions. The telephone survey did not reveal any disparity in the medical records. CONCLUSION: With experienced surgeons and anesthetists in a suitable specialist hospital, external dacryocystorhinostomy in preschool children would appear to be a safe and effective procedure, with few and minor complications. Although facilities for overnight observation should be available, the surgery can typically be planned as a day-case admission, and simultaneous bilateral surgery is also possible in this age-group.

Perioperative Prophylactic Antibiotics in 1,250 Orbital Surgeries.

PURPOSE: Intravenous antibiotic prophylaxis is used for many clean-contaminated surgeries or clean surgeries with an implant, but its value for clean orbital surgery has not been determined. This study investigated infection risks and adverse effects related to antibiotics in patients undergoing orbital surgery. METHODS: A prospective, nonrandomized comparative case series of all patients undergoing orbital surgery with participating surgeons between October 1, 2013, and March 1, 2015. Types of surgery, antibiotic regimens, corticosteroid use, antibiotic side effects, and surgical site infections (SSIs) were entered into an electronic database and subsequently analyzed. Cases in which patients received postoperative oral antibiotics were analyzed separately. RESULTS: Of 1,250 consecutive orbital surgeries, 1,225 met inclusion criteria. A total of 1208 patients were included in the primary analysis: 603 received no antibiotic prophylaxis (group A), and 605 received a single dose of intravenous antibiotic (group B). Five patients (0.42%) developed an SSI, 3 in group A and 2 in group B. The difference in SSI rates was not statistically significant between the 2 groups (p = 0.66). Antibiotic prophylaxis, alloplastic implants, paranasal sinus entry, and corticosteroid use were not associated with differences in SSI rates. All SSIs resolved on a single course of oral antibiotics; an implant was removed in 1 case. There were no complications associated with a single dose of intravenous prophylaxis. However, 12% of 17 patients (group C) who received 1 week of oral postoperative prophylactic antibiotics developed antibiotic-related complications (diarrhea, renal injury), yielding a number needed to harm of 8.5. CONCLUSIONS: In this large series, antibiotic prophylaxis does not appear to have reduced the already low incidence of SSI following orbital surgery. Given the detriments of systemic antibiotics, the rarity of infections related to orbital surgery, and the efficacy of treating such infections should they occur, patients undergoing orbital surgery should be educated to the early symptoms of postoperative infection and followed closely, but do not routinely require perioperative antibiotics.

Ocular amyloid: adnexal and systemic involvement.

Purpose: To investigate the natural history of ocular adnexal and orbital amyloidosis.Methods: In a retrospective, non-comparative case series, the clinical records of patients with biopsy-proven ocular, adnexal, and orbital amyloidosis managed at our institution between 1980 and 2016 were evaluated.Results: Forty-one patients (29 female; 71%) were identified. The mean interval from presentation to diagnosis was 24 months (median 12 months, range 1-84 months). Whilst most patients presented with a conjunctival mass (34/41; 83%) or ptosis (15/41; 37%), the diagnosis was not immediately evident in all - two patients had 3 ptosis operations prior to obtaining a tissue biopsy that revealed amyloid deposition. Three-quarters (31/41; 76%) of patients had localised primary ocular adnexal and orbital amyloidosis, 4 (10%) had associated systemic disease, and 6 (15%) were found to have underlying haematological malignancy on further investigation. During a mean follow-up of 8 years (median 7 years; range 6 months - 36 years), 2 (5%) patients lost vision, 21 (51%) had surgical intervention other than biopsy, and 2 (5%) had local radiotherapy for amyloid deposition secondary to lymphoproliferative disease.Conclusions: The varied presentations of ocular adnexal and orbital amyloidosis and the need for confirmatory biopsy often leads to a significant delay between first symptoms and diagnosis. While rarely sight-threatening, ocular adnexal and orbital amyloidosis carries significant morbidities and has a systemic association in a quarter of patients.

Detection of mutations in SF3B1, EIF1AX and GNAQ in primary orbital melanoma by candidate gene analysis.

BACKGROUND: Ocular melanoma is a rare but often deadly malignancy that arises in the uvea (commonest primary site), conjunctiva or the orbit. Primary orbital melanoma (POM) is exceedingly rare, with approximately 60 cases reported to date. Despite recent advances in our understanding of the genetics of primary uveal and conjunctival melanomas, this information is lacking for POM. METHODS: DNA was extracted from 12 POM tissues, with matched germline DNA (where available). MLPA was conducted to detect chromosomal alterations and Sanger sequencing used to identify point mutations in candidate melanoma driver genes (BRAF, NRAS, KRAS, GNA11, GNAQ), and other genes implicated in melanoma prognosis (EIF1AX, SF3B1). Immunohistochemistry was performed to analyse BAP1 nuclear expression. RESULTS: MLPA detected copy number alterations in chromosomes 1p, 3, 6 and 8. Sequencing of melanoma driver genes revealed GNAQ (p.Q209L) mutations in two samples; although it is possible that these samples represent extraocular spread of an occult uveal melanoma. A recurrent mutation in SF3B1 (p.R625H) was observed in indolent, but not aggressive, tumours; a mutation in EIF1AX (p.N4S) was detected in one patient with non-aggressive disease. CONCLUSIONS: EIF1AX and SF3B1 mutations appear have a role in determining the clinical course of POM and detection of these changes could have clinical significance. Further in depth analysis of this rare group using differing 'omic technologies will provide novel insights into tumour pathogenesis.

Orbital Inflammation as a Presenting Sign for CREST Syndrome.

A 61-year-old male was referred with a week's history of a painful and swollen left eye. Examination revealed normal visual acuities, left proptosis and global restriction of ocular ductions, and subretinal fluid at the macula. CT imaging confirmed thickening of the posterior scleral coat, with an associated choroidal effusion. Serology revealed positive antinuclear antibodies with a centromere staining pattern; subsequent rheumatology review revealed extensive telangiectasia with digital ulceration in both hands, and a diagnosis of limited cutaneous systemic sclerosis was made. Orbital inflammatory disease is often the initial presentation of systemic diseases such as sarcoidosis, granulomatosis with polyangiitis, and IgG4 disease. Limited cutaneous systemic sclerosis is rarely encountered in the context of orbital inflammation, but is a further systemic association, reminding the clinician of the diagnostic importance of peripheral symptoms and serological markers in patients presenting with orbital inflammation and scleritis.

Magnetic Oculomotor Prosthetics for Acquired Nystagmus.

PURPOSE: Acquired nystagmus, a highly symptomatic consequence of damage to the substrates of oculomotor control, often is resistant to pharmacotherapy. Although heterogeneous in its neural cause, its expression is unified at the effector-the eye muscles themselves-where physical damping of the oscillation offers an alternative approach. Because direct surgical fixation would immobilize the globe, action at a distance is required to damp the oscillation at the point of fixation, allowing unhindered gaze shifts at other times. Implementing this idea magnetically, herein we describe the successful implantation of a novel magnetic oculomotor prosthesis in a patient. DESIGN: Case report of a pilot, experimental intervention. PARTICIPANT: A 49-year-old man with longstanding, medication-resistant, upbeat nystagmus resulting from a paraneoplastic syndrome caused by stage 2A, grade I, nodular sclerosing Hodgkin's lymphoma. METHODS: We designed a 2-part, titanium-encased, rare-earth magnet oculomotor prosthesis, powered to damp nystagmus without interfering with the larger forces involved in saccades. Its damping effects were confirmed when applied externally. We proceeded to implant the device in the patient, comparing visual functions and high-resolution oculography before and after implantation and monitoring the patient for more than 4 years after surgery. MAIN OUTCOME MEASURES: We recorded Snellen visual acuity before and after intervention, as well as the amplitude, drift velocity, frequency, and intensity of the nystagmus in each eye. RESULTS: The patient reported a clinically significant improvement of 1 line of Snellen acuity (from 6/9 bilaterally to 6/6 on the left and 6/5-2 on the right), reflecting an objectively measured reduction in the amplitude, drift velocity, frequency, and intensity of the nystagmus. These improvements were maintained throughout a follow-up of 4 years and enabled him to return to paid employment. CONCLUSIONS: This work opens a new field of implantable therapeutic devices-oculomotor prosthetics-designed to modify eye movements dynamically by physical means in cases where a purely neural approach is ineffective. Applied to acquired nystagmus refractory to all other interventions, it is shown successfully to damp pathologic eye oscillations while allowing normal saccadic shifts of gaze.

Diagnosis of enlarged extraocular muscles: when and how to biopsy.

PURPOSE OF REVIEW: To review current knowledge regarding diagnosis of nonthyroid orbital disorders with extraocular muscle enlargement. RECENT FINDINGS: Recent publications have focused on immunoglobulin G4-related disease as a possible cause of enlarged extraocular muscles, on patterns of strabismus that raise a clinical suspicion of intramuscular lymphoma, and on surgical techniques to access the muscles for tissue biopsy. SUMMARY: With enlarged extraocular muscles, features to distinguish between competing diagnostic possibilities are based on imaging in the context of history and clinical signs. Infraorbital nerve enlargement in the presence of muscle enlargement strongly favours a diagnosis of immunoglobulin G4-related disease and reactive lymphoid hyperplasia. As our understanding of minimally invasive orbital surgery evolves, the diagnostic focus is shifting toward earlier identification through muscle biopsy.

Unusual selection on the KIR3DL1/S1 natural killer cell receptor in Africans.

Interactions of killer cell immunoglobulin-like receptors (KIRs) with major histocompatibility complex (MHC) class I ligands diversify natural killer cell responses to infection. By analyzing sequence variation in diverse human populations, we show that the KIR3DL1/S1 locus encodes two lineages of polymorphic inhibitory KIR3DL1 allotypes that recognize Bw4 epitopes of protein">HLA-A and HLA-B and one lineage of conserved activating KIR3DS1 allotypes, also implicated in Bw4 recognition. Balancing selection has maintained these three lineages for over 3 million years. Variation was selected at D1 and D2 domain residues that contact HLA class I and at two sites on D0, the domain that enhances the binding of KIR3D to HLA class I. HLA-B variants that gained Bw4 through interallelic microconversion are also products of selection. A worldwide comparison uncovers unusual KIR3DL1/S1 evolution in modern sub-Saharan Africans. Balancing selection is weak and confined to D0, KIR3DS1 is rare and KIR3DL1 allotypes with similar binding sites predominate. Natural killer cells express the dominant KIR3DL1 at a high frequency and with high surface density, providing strong responses to cells perturbed in Bw4 expression.

Clinical and Imaging Features of Lacrimal Gland Involvement in Granulomatosis with Polyangiitis.

PURPOSE: Lacrimal gland involvement in granulomatosis with polyangiitis (GPA) commonly accompanies orbital disease, but occasionally may be the sole presentation preceding any other organ manifestation or systemic disease. Diagnosis of orbital GPA, especially in patients with lacrimal involvement as the initial presentation, can be difficult because of nonspecific clinical features and lack of diagnostic specificity on histologic and antineutrophilic cytoplasmic antibody (ANCA) testing. Orbital GPA can be associated with a high morbidity from potential visual loss or rapid progression of latent systemic disease, making early diagnosis important. The purpose of this study was to describe the clinical and imaging features of patients with lacrimal gland involvement secondary to GPA and to compare them with those of other orbital inflammatory conditions in the lacrimal gland fossa. DESIGN: Retrospective, noninterventional comparative case series. PARTICIPANTS: Two hundred forty-seven patients who had undergone orbital biopsy over a 21-year period were identified from the Institute of Ophthalmology Pathology database. Sixty-nine patients were found to have orbital inflammatory disease with lacrimal gland involvement, of whom 7 had a final diagnosis of GPA. METHODS: Clinical and imaging features of patients with GPA were analyzed and compared with those of the non-GPA group. MAIN OUTCOME MEASURES: Features associated with GPA. RESULTS: The median age at presentation for GPA patients was 30 years (mean ± standard deviation, 36.7±16.7 years; range, 14-57 years). The interval from presentation to definitive diagnosis of GPA ranged from 3 to 20 months (mean, 12.1 months; median, 12 months). Sinonasal involvement was demonstrated in 43% and bony changes were demonstrated in 29% of patients with GPA. A higher proportion of patients with GPA demonstrated sinonasal involvement (P = 0.011) and bony destruction (P = 0.048) compared with non-GPA patients. CONCLUSIONS: Associated sinonasal involvement and bony changes on imaging are highly suggestive of GPA and should prompt a full diagnostic workup. A high index of suspicion should be maintained, with repeated ANCA testing, biopsy, and imaging where indicated, especially in the younger age group.