Systemic Involvement in Immunoglobulin G4-Related Ophthalmic Disease.

BACKGROUND: Immunoglobulin G4-related ophthalmic disease (IgG4-ROD) poses clinical challenges due to its heterogeneous ocular and systemic manifestations. We aim to report the systemic involvement and the clinical, serological and radiological associations of a cohort of Chinese patients. METHODS: A territory-wide, biopsy-proven, Chinese cohort. A retrospective, masked chart review of medical records, orbital images, and histopathology reports. RESULTS: A total of 122 (65 male) patients with a follow-up of 81 ± 49 (24 to 84) months were reviewed. Ninety (74%) patients presented bilaterally. Subacute upper eyelid swelling was the commonest presentation (82/122, 67%). During follow-up, 91/122 patients (75%) underwent extra-orbital imaging including computer tomography (692 films), ultrasonography (182 films), magnetic resonance imaging (76 films) and whole body FDG-PET scan (33 films). Eighty-six (95%) of these 91 patients had extra-orbital involvement radiologically (2.7 ± 1.6 regions, range: 0 to 9). Lymph node was the most prevalent (N = 60,66%), followed by salivary gland (N = 51,56%), lung (N = 49,54%), kidney (N = 22, 24%), hepatobiliary tree (N = 18, 20%) and pancreas (N = 17, 19%). Other organs include thyroid, aorta, meninges/brain and skin. Twenty-eight (23%) patients had allergic diseases (19 asthma, 16 allergic rhinitis, and 6 eczemas). Fifty-seven (48%) patients had paranasal sinusitis. Serum eosinophilia was associated with a higher number (3.24 versus 2.52, P = 0.0304) of organ involvement. Patients with deep organ involvement was associated with a higher age of IgG4-ROD onset (70 ± 12 versus 56 ± 13, P < 0.0001). CONCLUSIONS: 95% of the patients who underwent systemic imaging in our cohort had systemic organ involvement. An early physicians' assessment and radiological imaging are recommended after the diagnosis of IgG4-ROD.

Ocular Surface Evaluation in Immunoglobulin G4-Related Ophthalmic Disease.

PURPOSE: To evaluate the functional and structural changes of the meibomian glands and ocular surface in immunoglobulin G4-related ophthalmic disease (IgG4-ROD) patients. DESIGN: Cross-sectional, matched case-control comparison study. METHODS: This study included 64 patients with biopsy-proven IgG4-ROD (aged 63.4 ± 12.2 years, 39 male) and 64 sex- and age-matched healthy controls. Patients were managed by hospitals covering the publicly funded ophthalmology service in Hong Kong. Outcome measures included anterior segment examination and keratographic and meibographic imagings. RESULTS: A total of 64 worst-affected eyes of the 64 IgG4-ROD patients were analyzed. Corneal fluorescein staining (P = .0187), lid margin telangiectasia (P = .0360), lid-parallel conjunctival folds (P = .0112), papillae (P = .0393), meibomian gland plugging (P = .0001), meibomian gland expressibility (P = .0001), and meibum quality (P = .0001) were more significant in IgG4-ROD patients compared with healthy controls. Both upper and lower meibomian gland dropouts (P = .001 and .0003), and tear meniscus height (P = .0001) were higher in IgG4-ROD patients. Non-invasive tear break-up time (NITBUT) (P = .0166) and Schirmer test results (P = .0243) were lower in IgG4-ROD patients. Upper (r = 0.336, P = .0140) meibomian gland dropouts and NITBUT (r = -0.293, P = .0497) were positively and negatively correlated with the IgG4-ROD onset age, respectively. The number of extraocular organ involvement was negatively correlated with the Schirmer test(r = -0.341, P = .0167). Lower NITBUT was found in IgG4-ROD eyes with lacrimal gland enlargement than in IgG4-ROD eyes without lacrimal gland enlargement radiologically (P < .0001). CONCLUSIONS: IgG4-ROD patients showed features of both aqueous tear deficiency and evaporative dry eye disease. We recommend ocular surface evaluation to all patients newly diagnosed with IgG4-ROD. Further studies are warranted to clarify the mechanism of IgG4-related dry eye disease.

Malignancies in Immunoglobulin G4-related ophthalmic disease.

PURPOSE: Clinical phenotypes in Immunoglobulin G4-related disease (IgG4-RD) according to the patterns of affecting organs have different risks of malignancies. We attempt to determine the association of malignancies with IgG4-related ophthalmic disease (IgG4-ROD). DESIGN: Retrospective cohort study. METHODS: Review of medical records, orbital images and histopathology reports in a territory-wide cohort of biopsy proven IgG4-ROD patients from 2005-2019. FINDINGS: Among 122 patients who had biopsies taken from adnexal lesions including lacrimal glands (n = 108), orbital mass (n = 30), infiltrated orbital fat (n = 10), conjunctiva (n = 2) or extraocular muscles (n = 3), 13% (16/122) developed malignancies over 73 ± 48months' follow-up. There were 9 cases of ocular adnexal lymphoma (OAL) and 7 extra-orbital malignancies. Compared with the general population, the incidence of OAL was significantly higher (standardized incidence ratios, SIRs = 10.0, 95%CI = 4.5-17.6) while that of extra-orbital malignancies was similar. The SIRs was highest within the first year (SIR = 46.7, 95%CI = 18.5-87.6) when 7 OAL were concomitantly diagnosed. Patients who developed OAL or extra-orbital malignancies were older than other patients at IgG4-ROD diagnosis (64.9 ± 7.1, 68.3 ± 8.5 versus 55.2 ± 15.0 years, P < 0.05). Asymmetric lacrimal gland enlargement (78% versus 13%), lack of frontal (0% versus 12%) or infraorbital nerve enlargement (0% versus 36%) were associated with OAL (all P < 0.05). Pre-treatment serum IgG4 level or extra-orbital IgG4-RD involvement was similar among patients with or without malignancies. CONCLUSION: In this biopsy-proven IgG4-ROD cohort, 7% developed OAL which was 10 times higher than the general population. Patients with asymmetric lacrimal gland enlargement or without trigeminal nerves involvement radiologically were associated with OAL.

Treatment outcomes and their determinants of IgG4-related ophthalmic disease: a territory-wide cohort study.

BACKGROUND: Oral corticosteroid remains the first-line treatment of IgG4-related ophthalmic disease, but steroid-dependence is common and serious. Factors associated with steroid dependence and relapse have to be further explored. STUDY POPULATION: A city-wide, biopsy-proven, Chinese cohort. METHODS: Retrospective, masked review of medical records, orbital images and histopathology reports. RESULTS: There were 101 patients with at least 24-month follow-up. Up to 82% (82/101) received oral corticosteroid as first-line treatments, and 7 of them received also concomitant steroid-sparing agents (SSA)/biological agents as primary treatment. There was 61% (50/82) of patients required long-term corticosteroid (alone=23, with SSA=27) after 1.9±0.7 (range 1-5) relapses. When compared with the 21% (17/82) of patients who tapered corticosteroid successfully for 24 months, steroid dependence was associated with elevated baseline serum IgG4 level (94% vs 65%, p<0.01) and Mikulicz syndrome (46% vs 18%, p<0.05). Up to 13% (11/82) of patients tolerated residual disease after tapering off corticosteroid. There was 17% (17/101) of patients did not require any medications after biopsies. They were more likely to have debulking surgeries (71% vs 40%, p<0.05), discrete orbital lesions (65% vs 26%, p<0.05), normal baseline serum IgG4 level (24% vs 6%, p<0.05) and no Mikulicz syndrome (94% vs 61%, p<0.05). CONCLUSION: In this cohort, 60% of patients required long-term maintenance oral corticosteroid. Elevated pretreatment serum IgG4 level and Mikulicz syndrome were associated with steroid dependence. Debulking surgery is an alternative for a subgroup of patients with discrete orbital lesions, normal baseline IgG4 level and no Mikulicz syndrome.

Radiological Determinants of Complicated Immunoglobulin G4-Related Ophthalmic Disease: A Territory-Wide Cohort Study.

PURPOSE: To evaluate the presenting radiological features of immunoglobulin G4-related ophthalmic disease (IgG4-ROD) and their associations with IgG4-related optic neuropathy (IgG4-RON), and IgG4-related ocular adnexal lymphoma (IgG4-ROL). METHODS: A territory-wide, biopsy-proven, Chinese cohort. Masked review of orbital images, medical records, and histopathology reports. RESULTS: A total of 115 (94%) of the 122 patients in our cohort had preoperative orbital images (computed tomography=105, magnetic resonance imaging=40). Among them, 103/115 (90%) showed enlarged lacrimal glands, and 91 (88%) were bilateral. Nerve enlargement was observed: infraorbital in 31/115 (27%) patients and frontal in 17/115 (15%), 10 and 9 being bilateral, respectively. At least 1 or more extraocular muscle (EOM) enlargement was found in 41/115 (37%) patients, bilaterally in 20. Lateral rectus occurred in 30 (73%) of these 41 EOM patients and inferior rectus in 28 (68%). Two adjacent EOMs (inferior and lateral recti in 11 patients, inferior and medial recti in 7 patients) or multiple EOMs (at least 3) were enlarged in 23/41 (56%) and 13/41 (32%) of the patients, respectively. Intraconal lesions (67% vs 11%, P<0.05), infraorbital (83% vs 23%, P<0.005), or frontal (50% vs 15%, P<0.05) nerve enlargement was significantly associated with IgG4-RON (6 patients) by univariate analyses. Asymmetric lacrimal gland enlargement and discrete orbital mass (both P<0.05) were associated with IgG4-ROL (9 patients) by multivariate analyses. CONCLUSIONS: In this IgG4-ROD cohort, most patients had bilateral enlarged lacrimal glands, and the lateral rectus is the most frequently involved EOM. For the first time, unique radiological patterns associated with the development of IgG4-RON and IgG4-ROL are found.

Proceedings of the Neuro-Ophthalmology Program of the 33rd Asia-Pacific Academy of Ophthalmology Congress, Hong Kong, 8-11 February 2018.

The 33rd Asia-Pacific Academy of Ophthalmology (APAO) Congress was held on Feb 8-11, 2018 in Hong Kong. This report summarized the highlights of the neuro-ophthalmology program of the Congress, including the scientific symposia (invited and submitted) and the social activities.

Optic Disc and Macular Imaging in Blind Eyes from Non-glaucomatous Optic Neuropathy: A Study with Spectral-domain Optical Coherence Tomography.

The purpose of this study was to determine and compare the optic disc and macular thickness measurements using two spectral-domain optical coherence tomography (SD-OCT) instruments in long-standing blind eyes diagnosed with non-glaucomatous optic neuropathies (NGON). A prospective observational case-series design was used. Twelve eyes from 12 NGON patients with no light perception for at least 6 months underwent optic disc and macular imaging with Cirrus HD-OCT and Spectralis OCT. The correlation between the peripapillary retinal nerve fibre layer (PRNFL) and macular ganglion cell layer and inner plexiform layer (GCL+IPL) thicknesses, and between the duration of no light perception (NLP) and PRNFL/GCL+IPL thicknesses were determined using Spearman's correlation analysis. The mean average PRNFL thickness was 55.9 ± 4.8 µm for Cirrus HD-OCT, which was significantly thicker than that measured by Spectralis OCT (31.9 ± 7.4 µm; p < 0.001). The mean central macular thickness on Cirrus HD-OCT was normal, but there was global thinning at the other macular areas. The mean average GCL+IPL thickness on Cirrus HD-OCT was 51.8 ± 5.8 µm. There was a good correlation between average PRNFL thickness and GCL+IPL thickness (r = 0.830, p = 0.002); however, there was no significant correlation between the duration of NLP to the average PRNFL thickness (on either instruments) or GCL+IPL thickness on Cirrus HD-OCT (p > 0.7). These results show that there was residual PRNFL thickness in NGON eyes with NLP, which varied significantly between SD-OCT instruments. The values of the residual PRNFL and GCL+IPL thicknesses in blind eyes (the "floor" effect) may be useful for prognostic purposes for patients with partial optic atrophy.

The Pathogenesis of Nonarteritic Anterior Ischemic Optic Neuropathy.

Although nonarteritic anterior ischemic optic neuropathy (NAION) is known to occur as a result of ischemic insult to the anterior portion of the optic nerve, its etiology and pathogenesis remain elusive. Because NAION is a nonfatal condition, acute, postmortem histopathologic analysis has never been undertaken. Animal models of NAION have been created with the use of an iodinated derivative of fluorescein, rose bengal. When rose bengal is stimulated with the use of a frequency-doubled neodymium-Yttrium aluminium garnet (YAG) laser diode, vascular endothelial damage may be induced in a precise and focal manner, within the anterior optic nerve. Primate and nonprimate animal models of NAION differ from the human pattern of NAION in the duration of the disease course, as well as the anatomy. The rat lamina cribrosa contains a differing connective tissue structure, which may result in a differing pathogenesis of ischemic insult. Optic disk swelling resolves within 5 days in rats and 14 days in primates; in humans, it is known to persist for up to 6 weeks. Animal models have nonetheless enabled a deeper understanding of the underlying pathologic processes in NAION.

Acute and subacute inflammation of the optic nerve and its sheath: clinical features in Chinese patients.

OBJECTIVE: Inflammation of the optic nerve (optic neuritis) and its sheath (optic perineuritis) can have similar initial clinical presentations. They are less well-defined in the Chinese than in Caucasians, and the aetiology of optic neuritis may also differ depending on ethnicity. The aim of our study was to document the clinical features of acute/subacute optic neuritis/optic perineuritis in Chinese patients. DESIGN: Retrospective case series. SETTING: Hong Kong Eye Hospital, Hospital Authority. PATIENTS: Records of all patients presenting to the Hong Kong Eye Hospital between 2005 and 2008, with their first episode of optic neuritis/optic perineuritis with onset of symptoms within 30 days, were reviewed. MAIN OUTCOME MEASURES: Disease aetiology, clinical features and outcomes. RESULTS: Twenty-nine patients were included (M:F=13:16), with a mean age of 46 years at presentation. Among these, 25 had optic neuritis and four had optic perineuritis; four presented with bilateral optic neuritis. Among the optic neuritis group, 17 (68%) were idiopathic, seven (28%) were related to multiple sclerosis, and one (4%) had neuromyelitis optica. Poor visual outcome in the optic neuritis group was associated with poor visual acuity at presentation and poor visual acuity at the nadir. CONCLUSION: Optic perineuritis and neuromyelitis optica-related optic neuritis were more commonly encountered in our study of Hong Kong Chinese patients than in Caucasian populations. Even in Chinese patients with 'typical' optic neuritis, neuro-imaging and further investigations may be warranted to exclude optic perineuritis/neuromyelitis optica, since Chinese ethnicity is itself an atypical feature. Where neuro-imaging is not readily available, intravenous methylprednisolone may be considered as initial treatment to cover both optic neuritis/optic perineuritis in patients with severe visual loss.

Limited nasal septoplasty by ophthalmologists during endonasal dacryocystorhinostomy: is it safe?

PURPOSE: Significant deviated nasal septum (DNS) may preclude the performance of endonasal dacryocystorhinostomy (DCR). The purpose of this study was to investigate the outcomes of limited nasal septoplasty in tackling signficant DNS performed by trained ophthalmologists during endonasal DCR. METHODS: In this retrospective interventional case series, the records of all patients requiring limited nasal septoplasty for significant DNS during endonasal DCR at 2 tertiary ophthalmic centers in Hong Kong during January 2006 to December 2007 were reviewed. Surgical outcomes, demographic factors, and intraoperative and postoperative details were recorded and analyzed. RESULTS: A total of 25 septoplasties were performed in 25 patients (total of 28 DCR). After the nasal septoplasty, all nasal cavities had better exposure of the surgical site allowing completion of the endonasal DCR. At the latest follow-up, the anatomical and functional success rates of the endonasal DCR were both 96.4% (27/28). In one patient, septoplasty was complicated by asymptomatic mucosal adhesion between the lateral nasal wall and the nasal septum. CONCLUSIONS: In the hands of trained ophthalmic lacrimal surgeons, limited nasal septoplasty is an effective and safe procedure during endonasal DCR, allowing better exposure of the surgical field in patients with significant DNS.

Late-onset occult cerebrospinal fluid leakage after orbital exenteration.

Orbital exenteration can be complicated by cerebrospinal fluid leakage, mostly during surgery. Late-onset cerebrospinal fluid leakage that occurs years after the initial orbital exenteration is rare. The authors report a case of cerebrospinal fluid leakage that occurred 4 years after orbital exenteration that was not due to tumor recurrence. The leakage was managed successfully by the application of cyanoacrylate tissue glue. No complication was encountered.

Surgical anatomy of the Chinese orbit.

PURPOSE: To describe the metric measurements and normal anatomic variants in Chinese bony orbits. METHODS: Orbital osteology was studied in 194 orbits from 97 Chinese skulls. Morphologic observations and metric measurements were made to elucidate the variations of the orbital bony anatomy and to localize important fissures and foramina within the orbit. Sexual dimorphism and side asymmetry of orbital features were analyzed. Results were then compared with data from other populations. RESULTS: The details of the orbital osteology in Chinese are described. Most orbital features show anatomic variations in terms of their existence, quantity, and location. Anatomic variants including quadruple and extrasutural posterior ethmoidal foramen are described for the first time. Side asymmetry and sexual dimorphism (male larger than female) are demonstrated in some orbital features. Compared with white and American populations, orbital measurements are generally smaller in Chinese, probably related to their smaller orbital size. CONCLUSIONS: The Chinese orbital osteology demonstrates considerable variability. The newly described anatomic variants found on the posterior ethmoidal foramen may affect surgical procedures related to the medial orbital wall. Sexual dimorphism and ethnic variations of the orbital bony anatomy may affect surgical approach to orbital diseases in different populations.

Quality of reporting of key methodological items of randomized controlled trials in clinical ophthalmic journals.

PURPOSE: To evaluate the reporting quality of key methodological items in randomized controlled trials (RCTs) in four general clinical ophthalmology journals. METHODS: The reporting of 11 key methodological items in RCTs published in American Journal of Ophthalmology, Archives of Ophthalmology, British Journal of Ophthalmology and Ophthalmology in the year 2005 was assessed. RESULTS: Sixty-seven eligible RCTs were assessed and the mean number of items reported was 6.3 per RCT. No significant difference in the mean number of items reported was found between the four journals (P=0.20). The most frequently reported item was ethics approval and informed consent (97.0%), followed by masking status (85.1%), description of withdrawals (76.1%), adverse events (73.1%), and intention-to-treat analysis (71.6%). Details on sequence generation, randomization restriction, allocation concealment, allocation implementation, patient flow diagrams, and sample size calculation were reported in <50% of the RCTs assessed. Both sample size and page length of the RCTs correlated with the number of methodological items reported (P=0.024 and P=0.008, respectively). CONCLUSIONS: Similar to other specialties, rooms for improvement exist in the reporting of key methodological items of RCTs in clinical ophthalmic journals. Stricter adoption of the CONSORT statement might enhance the reporting quality of RCTs in ophthalmic journals.

Retention of silicone oil droplets from ophthalmic viscosurgical devices in the drainage angle of 2 eyes.

We report the outcome in 2 eyes of 2 patients with retained silicone oil droplets in the anterior chamber drainage angle after the use of an ophthalmic viscosurgical device (OVD) during cataract surgery. Silicone oil droplets were observed when the OVD was injected into the anterior chamber during phacoemulsification. Despite removal by irrigation and aspiration, droplets were observed in the anterior chamber during the immediate postoperative period. At 15 months, they were observed in the drainage angle. The retained silicone did not produce untoward side effects in the eyes. Silicone oil is a common contaminant in OVDs but appears to be inert and harmless when retained in small amounts in the anterior chamber drainage angle.

Malignant oncocytoma of the lacrimal sac as an unusual cause of epiphora.

A 72-year-old man presented with a 2-year history of epiphora. CT revealed an extensive inferomedial orbital tumor connected to the lacrimal sac and duct. Incisional biopsy revealed malignant oncocytoma of the lacrimal sac. The patient was treated with exenteration and maxillectomy followed by a course of postoperative radiotherapy. Patients with malignant oncocytoma may present with simple epiphora in absence of other signs and symptoms such as blood stained tearing or purulent rhinorrhea.

Characterization and localization of the supraorbital and frontal exits of the supraorbital nerve in Chinese: an anatomic study.

PURPOSE: To elucidate the characteristics and location of the supraorbital and frontal exits of the supraorbital nerve in Chinese skulls and to compare these findings with other ethnic populations. METHODS: The anatomy of the supraorbital nerve exits was studied in 97 adult Chinese skulls (194 orbits). The characteristics and location of the supraorbital nerve exits were determined. Analyses were performed to compare differences between sexes and sides. Data were then compared with those of the other populations. RESULTS: Supraorbital exits were found in all 194 orbits. Among these, 89 (45.9%) were foramina. Frontal exits were found in 69 of the 194 (35.6%) orbits in which 18 were foramina (9.3%). The location of the supraorbital exits showed a skewed distribution toward the medial aspect of the superior orbital rim. The median distance between the supraorbital exits and the facial midline was 24.56 mm. Eighty percent of the supraorbital exits lay between 20.77 mm and 30.52 mm from the facial midline. The mean frontal exit was 7.02 mm medial to the supraorbital exits. Compared with other populations, a higher proportion of Chinese have foramina above the superior orbital rim as the exits for the supraorbital neurovascular bundle. The location of the supraorbital nerve exit is highly variable in all studied populations. CONCLUSIONS: In a significant proportion of Chinese, the supraorbital nerve exits are located toward the medial aspect of and above the superior orbital rim. Extra care should be taken during dissection around this region to avoid damage to the supraorbital nerve.

How evidence-based are publications in clinical ophthalmic journals?

PURPOSE: To evaluate the methodological quality and level of evidence of publications in four leading general clinical ophthalmology journals. METHODS: All 1919 articles published in the American Journal of Ophthalmology, Archives of Ophthalmology, British Journal of Ophthalmology, and Ophthalmology in 2004 were reviewed. The methodological rigor and the level of evidence in the articles were rated according to the McMaster Hedges Project criteria and the Oxford Centre for Evidence-Based Medicine levels of evidence. RESULTS: Overall, 196 (24.4%) of the 804 publications that were included for assessment met the Hedges criteria. Articles on economics evaluation and those on prognosis achieved the highest passing rate, with 80.0% and 74.4% of articles, respectively, meeting the Hedges criteria. Publications on etiology, diagnosis, and treatment fared less well, with respective passing rates of 28.3%, 20.2%, and 14.7%. Published systematic reviews and randomized controlled trials were uncommon in the ophthalmic literature, at least in these four journals during 2004. According to the Oxford criteria, 57.6% of the articles were classified as level 4 evidence compared with 18.1% classified as level 1. Articles on prognosis had the highest proportion (43.0%) rated as level 1 evidence. Generally, articles that reached the Hedges threshold were rated higher on the level-of-evidence scale (Spermans rho = 0.73; P < 0.001). CONCLUSIONS: The methodological quality of publications in the clinical ophthalmic literature was comparable to that in the literature of other specialties. There was substantial heterogeneity in quality between different types of articles. Future methodological improvements should focus on the areas identified as having the largest deficiencies.