Unsuspected and misdiagnosed posterior uveal melanoma following enucleation and evisceration in Ottawa-Gatineau.

OBJECTIVE: There is a gap in the recent literature on the topic of clinically misdiagnosed and unsuspected posterior uveal melanomas (PUM) with a calculation of the frequency of these events for a specific geographical area. As the only ophthalmic pathology laboratory in our region, we determined the rate of these outcomes over a 16-year period. METHODS: We retrospectively reviewed 2558 consecutive ophthalmic pathologic specimens in the Ottawa-Gatineau region, of which 334 were eviscerations and 227 were enucleations. We calculated the frequency of clinically misdiagnosed PUM and of clinically unsuspected PUM. We also determined the rate of uveal melanoma undergoing enucleation. RESULTS: From 100 diagnoses of PUM, 2 (2.0%) cases were clinically unsuspected and 2 (2.0%) cases were clinically misdiagnosed. The rate of uveal melanoma undergoing enucleation was 5.6 cases per 1 000 000 of population per annum. From 2009 to 2012, the incidence of this event was 3.8 cases per 1 000 000 per annum, which was lower than the previous three 4-year increments. CONCLUSIONS: We present the first and only single-centred, population-based data on the rates of unsuspected PUM and of clinical misdiagnosis of PUM in the era of modern diagnostic imaging. Our rate of clinical misdiagnosis is within the range of recent reports of this event. Unsuspected PUM occurred at a rate substantially lower than previously published. The incidence of uveal melanoma undergoing enucleation has decreased despite an increase in population, which reflects a shift in management from enucleation to radiation therapy.

Development of a predictive model for temporal artery biopsies.

OBJECTIVE: Temporal artery biopsy is a critical, relatively safe, and reliable test in the diagnosis of temporal arteritis. Yet, a clarification of the pre-test probabilities may provide clarity on which patients with suspected giant cell arteritis would benefit from this invasive diagnostic procedure. DESIGN: A prospective case series PARTICIPANTS: A consecutive case series of patients referred to the Ophthalmology service for temporal artery biopsy. METHODS: All subjects underwent standardized serum testing, and signs and symptoms assessment. Predictive models were created and evaluated. RESULTS: 119 patients were analyzed. This exploratory study found that a simple model including platelet count, erythrocyte sedimentation rate, and c-reactive protein was able to define a subset of patients with a pre-test probability of a positive biopsy of 0% or 100%. 40% (95% confidence interval 31%-49%) of patients fell into this category. CONCLUSIONS: Utilizing a simple clinically applicable predictive model of the pretest probability of a temporal artery biopsy in patients with suspected giant cell arteritis, up to 31%-49% of temporal artery biopsies may be avoided. This study was a single site exploratory study with data-driven thresholds - therefore these results need to be validated with an independent sample prior to clinical use.

Multivariable prediction model for suspected giant cell arteritis: development and validation.

PURPOSE: To develop and validate a diagnostic prediction model for patients with suspected giant cell arteritis (GCA). METHODS: A retrospective review of records of consecutive adult patients undergoing temporal artery biopsy (TABx) for suspected GCA was conducted at seven university centers. The pathologic diagnosis was considered the final diagnosis. The predictor variables were age, gender, new onset headache, clinical temporal artery abnormality, jaw claudication, ischemic vision loss (VL), diplopia, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and platelet level. Multiple imputation was performed for missing data. Logistic regression was used to compare our models with the non-histologic American College of Rheumatology (ACR) GCA classification criteria. Internal validation was performed with 10-fold cross validation and bootstrap techniques. External validation was performed by geographic site. RESULTS: There were 530 complete TABx records: 397 were negative and 133 positive for GCA. Age, jaw claudication, VL, platelets, and log CRP were statistically significant predictors of positive TABx, whereas ESR, gender, headache, and temporal artery abnormality were not. The parsimonious model had a cross-validated bootstrap area under the receiver operating characteristic curve (AUROC) of 0.810 (95% CI =0.766-0.854), geographic external validation AUROC's in the range of 0.75-0.85, calibration pH-L of 0.812, sensitivity of 43.6%, and specificity of 95.2%, which outperformed the ACR criteria. CONCLUSION: Our prediction rule with calculator and nomogram aids in the triage of patients with suspected GCA and may decrease the need for TABx in select low-score at-risk subjects. However, misclassification remains a concern.

Clinical predictors of positive temporal artery biopsy.

OBJECTIVE: We investigated the ability of known clinical signs and symptoms, as well as common laboratory tests, to correctly predict a positive temporal artery biopsy. DESIGN: A prospective cohort study. PARTICIPANTS: Consecutive patients in a tertiary referral centre undergoing temporal artery biopsy. METHODS: Clinical information was collected using a predesigned questionnaire. Pathology results and laboratory information were collected from digital patient records. MAIN OUTCOME MEASURE: The predictive value of clinical signs, symptoms, and laboratory values of a positive temporal artery biopsy. RESULTS: Over a 3-year period, 259 patients were enrolled and 251 patients were analyzed. Sixty-one patients had a positive biopsy. Clinical features most predictive of a positive biopsy were jaw claudication (positive likelihood ratio [LR+] 2.31) and abnormal temporal artery pulse (LR+ 2.62). Receiver operating characteristic curves generated for erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and platelets values showed an area under curve (AUC) value of 0.71, 0.75, and 0.76, respectively. The initiation of steroids decreased the diagnostic utility of the ESR, CRP, and platelets values (AUC = 0.58, 0.61, and 0.63, respectively). CONCLUSIONS: A variety of clinical signs and symptoms were observed in patients referred for a temporal artery biopsy. Clinical signs and symptoms were less accurate in predicting a positive biopsy than laboratory tests. No combination of clinical signs and symptoms tested was able to predict giant cell arteritis with the certainty necessary to justify or withhold long-term steroid therapy.

Secondary corneal amyloidosis after perforating corneal trauma: A series of 5 cases and review of the literature.

We retrospectively reviewed the clinical and surgical histories of 5 patients with traumatic secondary corneal amyloidosis, a relatively rare sequela of nonsurgical and surgical perforating corneal trauma. Four had history of nonsurgical trauma, and 1 had surgical trauma to the cornea. Three specimens were obtained by penetrating keratoplasties and 2 by excision of the cornea during evisceration of the ocular contents. All the corneal specimens showed full-thickness scars of a prior perforating wound with congophilic amyloid deposits that exhibited apple-green birefringence under polarized light and dichroism. All cases had variable degrees of predominantly chronic nongranulomatous inflammation. Ultrastructural examination in 1 patient disclosed 8-nm diameter fibrils in disarray, consistent with amyloid. Amyloid P immunostaining was positive in all 3 patients tested for this protein.

Incidence of discordant temporal artery biopsy in the diagnosis of giant cell arteritis.

OBJECTIVE: We investigated the rate of discordant biopsy results (i.e., 1 side negative, 1 side positive) in patients who underwent initial bilateral temporal artery biopsies for suspected giant cell arteritis (GCA). DESIGN: A cohort study. PARTICIPANTS: Consecutive patients undergoing temporal artery biopsy were enrolled. Of the 259 patients enrolled, 250 underwent initial bilateral temporal artery biopsies. METHODS: Positive biopsies were defined based on accepted histologic definitions. Healed arteritis was considered a positive result. Clinical information was collected for all patients using a questionnaire administered by an ophthalmologist. Pathology results, including biopsy length (as measured by the pathologist), and laboratory information (i.e., serum erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP] levels) were collected from digital patient records for statistical analysis. The main outcome was the rate of discordant biopsy in consecutive patients who underwent initial bilateral temporal artery biopsy. RESULTS: Giant cell arteritis was confirmed in 62 (24.2%) of the 250 patients, including 3 patients with biopsies recorded as healed arteritis. The rate of discordant biopsy was 4.4% with 11 unilaterally positive biopsies. There was no statistical difference between the length of the left- and right-sided biopsies in either the unilaterally or bilaterally positive groups (p = 0.13 and p = 0.79, respectively). The average maximum ESR value for the bilateral group (58.7 mm/h) was significantly higher than the average maximum ESR value for the unilateral group (30.7 mm/h, p = 0.03). The average maximum CRP value for the bilateral group was 59.2 mg/L and 28.6 mg/L for the unilateral group (p = 0.30). Discordance between the localization of symptoms and the side of positive biopsy occurred in 3 patients (i.e., 3 patients had left-sided symptoms only, yet a right-sided positive biopsy). CONCLUSIONS: The rate of discordant biopsies in patients who underwent initial bilateral temporal artery biopsies was considerable in our patient cohort. Given this reasonably high rate of discordance between sides, as well as the lack of correlation between side of positivity and laterality of presenting symptoms, we recommend initial bilateral temporal artery biopsies to enhance the diagnostic certainty of the disease.

Ocular metastasis of lung adenocarcinoma with ELM4-ALK translocation: A case report with a review of the literature.

Choroidal metastasis is the most common intraocular neoplasm and is associated with significant morbidity. In a small percentage of patients, ocular manifestation may be the initial presentation of a systemic malignancy and can be diagnostically difficult to distinguish from ocular primary malignancies. Herein, we present a case of a never-smoker whose ocular pathology was integral to the diagnosis and management of a lung adenocarcinoma harboring a rare oncogene. Through this case, we have explored important diagnostic and therapeutic considerations of pulmonary metastases to the choroid.

Myxomatous corneal degeneration: a clinicopathological study of six cases and a review of the literature.

Thirteen cases with myxomatous changes of the corneal stroma have been reported to date. We report six additional cases with clinical, histopathological, and immunohistochemical data. The clinical appearance is most often a gelatinous, whitish elevation with insidious onset. Histopathologically, there are inconspicuous spindle- and stellate-shaped cells in a loose, myxoid matrix. The typical location is in the anterior cornea beneath the epithelium, with varying degrees of extension into the stroma. Vimentin and smooth-muscle actin immunohistochemical stains are characteristically positive, and staining occasionally may be seen with muscle-specific actin, whereas CD34 staining usually is negative. In most cases, myxomatous changes are a degenerative process involving transformation of stromal keratocytes into cells with prominent secretory activity and myofibroblastic differentiation. Most occur in corneas with a history of ocular disease or trauma that disrupts Bowman's layer. We suggest labelling lesions with these features as "myxomatous corneal degeneration." So-called "primary corneal myxomas" also exist where there is no significant history. It remains unclear whether the myxomatous changes in such lesions are neoplastic or degenerative. Myxomatous corneal changes are likely under-recognized and under-diagnosed.

Conjunctival malignant melanoma: A rare variant and review of important diagnostic and therapeutic considerations.

Malignant melanoma of the conjunctiva is a relatively infrequent neoplasm that can be associated with significant morbidity and cause diagnostic difficulty to both the ophthalmologist and pathologist. We herein describe the first reported case in North American and European databases of a rare variant-signet ring cell melanoma - arising in the background of primary acquired melanosis (PAM) and use this case as a review of important diagnostic and therapeutic considerations when faced with this condition.

Histochemical analysis and immunohistochemical profile of mucoepidermoid carcinoma of the conjunctiva.

PURPOSE: To elucidate the distinct histochemical and immunohistochemical profile of mucoepidermoid carcinoma of the conjunctiva (MECC) and to determine which combination of stains is most useful in diagnosing MECC and differentiating it from squamous cell carcinoma of the conjunctiva (SCC) in cases where the clinical or cytological findings are not definitive. METHODS: Eight specimen of MECC from 4 patients and 4 specimens of SCC from 4 patients were examined using a variety of special stains and immunohistochemical markers. The results were then analyzed for usefulness in diagnosing MECC. RESULTS: The most useful markers in diagnosing MECC and differentiating it from SCC are mucicarmine, colloidal iron, and alcian blue all with sensitivities of 88%, and a specificity of 100%; CEA with a sensitivity of 83% and a specificity of 75%; and, mucin-1 with a sensitivity of 100% and a specificity of 25%, but which showed a distinct pattern of staining of MECC when compared to SCC. In our series, the sensitivity of the CK7+/CK20- combination for MECC was only 38%. CONCLUSIONS: The most useful stains in ruling out SCC in a suspected case of MECC were shown to be mucicarmine and the glycosaminoglycan (GAG) stains. However, in cases where mucicarmine and the GAG stains are negative or difficult to interpret and there is suspicion of a diagnosis of MECC, CEA and mucin-1 may be helpful for this diagnosis. The findings of CK7+/CK20- also may be of assistance, but are not as sensitive when compared to analogous salivary gland lesions, when differentiating MECC from SCC.

The bioceramic implant: evaluation of implant exposures in 419 implants.

PURPOSE: To compare the rate of exposure in the immediate 3-month postoperative follow-up period with the rate of exposure after the immediate postoperative period in 419 anophthalmic patients with a bioceramic (aluminum oxide) orbital implant. METHODS: This is a retrospective, clinical case series of 419 patients who received a bioceramic orbital implant. All patients who presented to five oculofacial surgeons (D.J., S.G., J.D., S.K., L.M.) from January 1, 2000, to June 1, 2007, who received a bioceramic orbital implant and had a minimum of 3 months of follow-up were included in this study. The authors analyzed age, gender, type of surgery, implant size, peg system, follow-up duration, time of pegging, and problems encountered. The data from the patients with greater than 3 months of follow-up with exposure of the bioceramic implant are detailed in this report. RESULTS: There were 353 patients followed for 3 to 96 months with an average of 30 months of follow-up (median 23 months). Implant exposure occurred in 32/353 bioceramic implants (9.1%). Six of the 32 (19%) exposures occurred during the 90-day postoperative period (average 2.1 months). Twenty-six (81%) exposures occurred outside of the 90-day postoperative period (average 27.5 months, range 4-82 months). CONCLUSIONS: Implant exposures can occur anytime postimplant placement. This review discovered an implant exposure rate of 9.1%, with the majority of the exposures occurring after the postoperative follow-up period. Patients with porous orbital implants should be followed on a long-term basis to detect this complication.

Lupus miliaris disseminatus faciei of the eyelids: report of two cases.

Lupus miliaris disseminatus faciei is a rare chronic, asymptomatic papular eruption, most commonly affecting the central face, including the eyelids. Our 2 patients presented with the typical clinical findings of small papular lesions in which histopathologic examinations disclosed granulomatous inflammation with necrosis associated with inflamed hair follicles. Except for its description as acne agminata by Duke-Elder in 1974, to the authors' knowledge, this condition has not been reported previously in the ophthalmic literature.

Pathogenesis of canalicular lacerations.

PURPOSE: To assess the pathogenesis of canalicular lacerations. METHODS: This is a retrospective, clinical case series of 236 patients who sustained a canalicular laceration. All patients who presented to the oculoplastic service of 3 individuals (D.R.J., S.M.G., L.A.M.) from May 1, 1998 to September 30, 2007, with a canalicular laceration were included in the study. Case histories were carefully reviewed in an attempt to classify the mechanism of injury as: "direct (penetrating) injury," "indirect (avulsive)," or "diffuse (avulsive)." Associated injuries (floor fractures, soft tissue lacerations, etc.) were also recorded. RESULTS: Of the 236 patients reviewed, direct canalicular injuries were detected in 128 (54.2%), indirect injuries were detected in 60 (25.4%), and diffuse injuries were detected in 48 (20.3%). Avulsive blunt injuries (due to indirect or diffuse trauma) therefore accounted for 45.7% of the lacerations whereas direct penetrating injuries accounted for 55.2% of the canalicular lacerations. Other injuries associated with the trauma occurred in 152 of the 236 patients (64%). Lacerations involving other portions of the eyelids, periocular area, and face made up the greatest number of associated injuries, and occurred with equal frequency in the direct penetrating group and the indirect/diffuse (avulsive injury) group. Associated injuries more serious in nature including orbital fractures, globe rupture, other body injuries, and head trauma were more commonly seen when diffuse trauma was involved. CONCLUSIONS: Direct, indirect, or diffuse forces may injure canaliculi but direct penetrating injuries were more common than avulsive injuries. More serious injuries (orbital fractures, globe rupture, other body injuries, and head trauma) were more commonly seen when diffuse trauma was involved.

The round-tipped, eyed pigtail probe for canalicular intubation: a review of 228 patients.

PURPOSE: To assess the effectiveness and outcomes of canalicular intubation with the use of a round-tipped, eyed pigtail probe. METHODS: Retrospective interventional case series of 228 patients requiring intubation of the canalicular system. Patients were treated surgically with attempted repair of the canalicular system with the round-tipped, eyed pigtail probe. The main outcome measures were successful intubation of the lacrimal system, symptoms of tearing, clinical functional evaluation of lacrimal system, complications, and need for further lacrimal surgery. RESULTS: Of 228 patients, 222 (97.4%) had their canalicular systems successfully intubated with silicone tubing using the round-tipped, eyed pigtail probe. Follow-up was obtained in 191 (86%) of the 222 patients. One-hundred sixty of 191 (83.8%) patients were irrigated and found to be anatomically patent (of the remainder, one was blocked whereas 30 were too young to be irrigated). One hundred fifty-two of the 191 (79.6%) patients had no tearing by history. Thirty-two (16.7%) had occasional tearing on some days that was not bothersome. Seven (3.7%) had intermittent or persistent tearing on a daily basis. Sixty-seven of the 191 (35%) had their lacrimal system more extensively assessed using the dye disappearance test, Jones I test, Jones II test, and canalicular probing. Anatomic patency in this subgroup was demonstrated in 66 of 67 (98.5%) of patients. The dye disappearance test, however, revealed slight asymmetry in 24 of 53 patients (45%) with canalicular lacerations yet only 14 of these 24 (58%) had any symptoms of tearing, indicating some discrepancy between subjective and objective assessment of tearing postcanalicular repair. Fifty-three of the repaired trauma patients underwent probing of the involved and uninvolved canalicular systems. In no patient was a stricture or blockage involving the uninvolved canaliculus identified. Additional lacrimal surgery (dacryocystorhinostomy) was performed on 2 of 191 (1%) patients with greater than 3 months follow-up. CONCLUSION: The round-tipped, eyed pigtail probe can help safely and effectively identify and repair canalicular lacerations. Symptomatic tearing was infrequent; the lacrimal systems showed complete anatomic patency in the majority of patients tested, and need for further lacrimal surgery was rare following pigtail probe intubation.

Orbital cholesterol granuloma and cholesteatoma: significance of differentiating the two.

Cholesteatoma and cholesterol granuloma are relatively rare lesions of the orbit. Both may involve the superior orbit and present with globe ptosis, proptosis, and double vision developing over weeks to years. In addition to their etiology being unknown, the nomenclature regarding these tumors historically has been confusing, with a variety of names being used to describe them. Their histopathology shares numerous similarities but has one key distinguishing feature: The cholesterol granulomas lack an epithelial lining, whereas the cholesteatomas have an epithelial lining. Surgical removal is the treatment of choice for both tumors. It is important to differentiate the two as the prognosis with recurrence differs. Cholesteatoma may recur with the possibility of malignancy found at the time of re-exploration. We present a case of each tumor type, illustrating their similarities and highlighting the histopathologic findings and treatment recommendations.

An unusual case of an enlarged temporal artery.

Giant cell arteritis (GCA) presents clinically as an enlarged, tender, non-pulsatile temporal artery with associated headache and systemic symptoms. We present an unusual case of a patient with an enlarged temporal artery in the absence of other clinical findings. An atypical biopsy result provided the diagnosis and guided treatment.

Lymphoproliferative lesions of the lacrimal gland: clinicopathological, immunohistochemical and molecular genetic analysis.

BACKGROUND: Lacrimal gland lymphoproliferative disorders are usually classified as orbital adnexal tumours. Because the lacrimal gland is the only orbital structure with native lymphocytes, we examined cases with primary involvement of the gland. METHODS: The 14 cases were selected from a review of all cases in the surgical pathology files of the Ottawa Hospital between 1992 and 2003. The lesions were categorized according to the latest World Health Organization classification of tumours of lymphoid tissues. We conducted a clinical, histopathological, immunohistochemical, immunophenotypic and molecular genetic analysis of the cases. RESULTS: The 8 female and 6 male patients, aged 20 to 88 (mean 60) years, were followed for an average of 4 years (range 11 months to 13 years). All presented with supratemporal orbital swelling. The 5 primary lymphomas, of mucosa-associated lymphoid tissue (MALT), were confined to the lacrimal gland (stage IE); 1 tumour transformed to diffuse large B-cell lymphoma, necessitating chemotherapy, and the other 4 were treated with radiation. One of the 5 patients had previously had Sjögren's syndrome. The 6 secondary lymphomas (4 follicular) presented either concurrently with systemic lymphoma or up to 12 years afterwards and were treated in a variety of ways; all the patients had an orbital relapse. At the last follow-up assessment, 6 of the patients with lymphoma had no evidence of disease, 3 were alive with disease, 2 had died (1 of lymphoma, the other with no evidence of disease), and the status of 1 patient was not known. Of the 3 patients with reactive proliferations, 2 had reactive lymphoid hyperplasia (associated with Sjögren's syndrome in 1), and 1 had Rosai-Dorfman disease. All 9 lymphomas that underwent molecular genetic analysis were of B-cell lineage, and 8 had a monoclonal rearrangement in the immunoglobulin heavy-chain gene (IgH); the 9th lymphoma showed an oligoclonal rearrangement. One lymphoma showed the t(14;18) translocation, typical of follicular lymphoma; no lymphoma showed the t(11;18) translocation, commonly found in MALT lymphoma (but only 2 cases were studied). Molecular genetic analysis was performed in 2 of the cases of reactive lymphoid hyperplasia: monoclonal IgH rearrangement was detected in 1 case (the patient with Sjögren's syndrome), oligoclonal rearrangement in the other. INTERPRETATION: Lacrimal gland lymphomas are B-cell tumours that develop in older adults. Primary tumours, a hIgH proportion of which have MALT characteristics, have a favourable prognosis. Molecular genetic studies may be useful when morphologic and immunophenotypic studies give equivocal results.

Behavior of various orbital implants under axial compression.

PURPOSE: To determine and compare the amount of force required to disrupt the integrity of various orbital implants. METHODS: Compression tests were carried out by using a servo-electrical universal testing system on orbital implants including aluminum oxide (Bioceramic implant, FCI, Issy-Les-Moulineaux, France), coralline hydroxyapatite (HA) (Bio-Eye, Integrated Orbital Implants, Inc., San Diego, CA, U.S.A.), bovine HA (Molteno M-Sphere, IOP Inc., Costa Mesa, CA, U.S.A.), synthetic HA (FCI3, FCI, Issy-Les-Moulineaux, France), Chinese HA (H + Y Comprehensive technologies, Philadelphia, PA, U.S.A.), polylactic acid (Kinsey Nash Corporation, Duluth, MN, U.S.A.), porous polyethylene (Medpor, Porex Surgical Inc., College Park, GA, U.S.A.), and polymethylmethacrylate. RESULTS: Two basic groups of implants were identified: those that eventually reach a critical compression point and collapse (coralline HA, aluminum oxide, synthetic FCI3 HA, bovine HA, Chinese HA, and polymethylmethacrylate), and those that do not collapse but gradually compress with increasing load (porous polyethylene, polylactic acid). For similar-sized implants, the critical collapse point was earliest for the FCI3 HA implant, followed by the coralline HA, aluminum oxide, and polymethylmethacrylate implants. Smaller-sized collapsible implants showed earlier critical collapse points than larger-sized implants of similar material. CONCLUSIONS: A technique was established to assess the force required to disrupt the integrity of various orbital implants that is reliable, unbiased, and repeatable with any orbital implant. Orbital implants of different materials and sizes demonstrate different degrees of integrity. It is important to use similar-sized implants when comparing the integrity of different implant materials because size influences the force required to overcome the structural integrity of the implant.