Treatment of keratoconjunctivitis sicca with topical androgen

Objective: Androgens have been reported to influence lipid production of sebaceous glands and even many ocular tissues. The effect of topical androgen therapy on a 54-year-old patient with keratoconjunctivitis sicca (KCS) and decreased lipid phase of the tear film is reported. Methods: For assessment of the lipid phase of the tear film, break up time (BUT) and lipid layer thickness (LLT) were monitored during 6 months before treatment as well as 3 months while using a daily topical androgen therapy. Results: During the topical androgen therapy the pathological lipid phase of the tear film was completely restored indicated by the normalisation of the values of BUT and LLT. Conclusion: These findings are consistent with animal experiments indicating that topical administered androgen can restore the decreased lipid phase of the tear film. This may open up new therapeutic strategies for KCS.     

Comparing the Discriminative Validity of Two Generic and One Disease-Specific Health-Related Quality of Life Measures in a Sample of Patients with Dry Eye

OBJECTIVE: The purpose of this study was to compare the discriminative properties of two generic health-related quality of life (QoL) instruments (SF-36 and EQ-5D) and a newly developed disease-specific patient-reported outcomes instrument (Impact of Dry Eye on Everyday Life (IDEEL)) to distinguish between different levels of dry eye severity. METHODS: Assessment of 210 people: 130 with non-Sjogren's Keratoconjunctivitis Sicca (non-SS KCS), 32 with Sj?gren's Syndrome (SS) and 48 controls; comparison of SF-36, EQ-5D, and IDEEL age-adjusted data by dry eye severity levels. Severity was assessed based on diagnosis (non-SS KCS, SS, control), patient-report (none, very mild, mild, moderate, severe, extremely severe) and clinician-report (none, mild, moderate, severe). RESULTS: Discriminative validity results were consistent for all instruments. Significant differences between severity levels were found with most SF-36 scales (P < 0.05), all EQ-5D scales (P < 0.05), and all IDEEL scales (P < 0.0001), except for Treatment Satisfaction. IDEEL scales consistently outperformed the generic QoL measures regardless of the severity criterion used. Most SF-36 scales outperformed the EQ-5D QoL scale, but the EQ-5D visual analog scale outperformed the SF-36 scales, except for General Health Perceptions. CONCLUSIONS: The disease-specific IDEEL scales are better able to discriminate between severity levels than the majority of the generic QoL scales. Preliminary evidence demonstrates that the IDEEL will be sensitive to QoL changes over time, although further testing in controlled longitudinal studies is needed.     

An experimental study of the management of severe keratoconjunctivitis sicca with autologous reduced-sized submandibular gland transplantation

We have evaluated transplantation of reduced submandibular glands for the treatment of severe keratoconjunctivitis sicca. Thirty-four rabbits were allocated into three groups: dry eye (controls, n=10), transplantation of whole submandibular glands (n=12), and transplantation of reduced submandibular glands (n=12). Outcome measures included the results of Schirmer's test and the Rose Bengal test, and histological examination of the cornea and the transplanted gland. Volume of tears significantly increased after transplantation of the whole gland, but did not change after transplantation of the reduced gland compared with dry eyes induced preoperatively. Neither transplantion group had keratoconjunctivitis sicca postoperatively. There were no histological abnormalities in the transplanted tissues. The results that the surgical technique of using reduced submandibular glands for transplantation was feasible, and that the secretion from the reduced gland was similar to that from a normal lacrimal gland. In conclusion, transplantation of a reduced submandibular glands is feasible in the treatment of keratoconjunctivitis sicca.     

Associations between ocular and extra-ocular assessment in primary Sjögren's syndrome*

ObjectivesTo assess associations between ophthalmological features and the main systemic biomarkers of primary Sjögren's Syndrome (pSS), and to identify systemic biomarkers associated with severe keratoconjunctivitis sicca (KCS) in pSS patients.MethodsIn this cross-sectional study, data was retrospectively extracted from the monocentric cohort of the French reference centre for pSS. We analysed data from the initial visit of patients admitted for suspicion of pSS and included patients validating pSS ACR/EULAR classification criteria. Ophthalmological assessment included Schirmer's test, tear break-up time, ocular staining score (OSS), and visual analogue scale (DED-VAS) for dry eye disease (DED) symptoms. Results of minor salivary gland biopsy, unstimulated whole salivary flow rate, anti-SSA/Ro antibodies, anti-SSB/La antibodies, and rheumatoid factor (RF) were collected.ResultsA total of 253 patients (245 females) with confirmed pSS, aged 56.6 ± 13.0 years, were included, among which 37% had severe KCS. Multivariate analysis showed that the presence of anti-SSA/Ro antibodies, anti-SSB/La antibodies and RF were associated with conjunctival OSS (odds ratio–OR– = 1.25 per OSS unit increase; confidence interval–CI–95% = 1.05–1.49; P = 0.01; OR = 1.31 per OSS unit increase; CI95% = 1.09–1.58, P = 0.002, and OR = 1.34 per OSS unit increase; CI95% = 1.12–1.59; P = 0.001, respectively). Both anti-SSB/La antibodies and DED-VAS ≥ 5 were significantly associated with severe KCS (OR = 2.03; CI95% = 1.03–4.00; P < 0.05 and OR = 2.52, CI95% = 1.31–4.90; P < 0.01, respectively).ConclusionAssociation between conjunctival OSS and systemic biomarkers of pSS indicate the crucial importance of conjunctival staining when pSS is suspected as a cause of DED. Conversely, patients with anti-SSB and DED-VAS ≥ 5 features should be prioritized for extensive evaluation by an ophthalmologist due to their association with severe KCS.     

Ableitende Tränenwege und Trockenes Auge

BACKGROUND: The knowledge regarding the pathogenesis, diagnosis, and treatment of dry eye has made large advances in recent years. However, many questions are still unanswered. Although the nasolacrimal ducts are part of the tear system they have been paid nearly no attention regarding dry eye. METHODS: The present knowledge about the nasolacrimal ducts is presented and discussed in a context with dry eye. A PubMED search was conducted for articles published from 1966 to the present; in addition, review articles as well as book chapters were considered and discussions with investigators in the field were performed. RESULTS: As a draining and secretory system, the nasolacrimal ducts play a role in tear transport and non-specific immune defense. Moreover, components of tear fluid are absorbed in the nasolacrimal passage and are transported into a vascular system that surrounds the nasolacrimal sac and nasolacrimal duct. This system is comparable to a cavernous body and it is connected to the blood vessels of the outer eye. Also it is subject to vegetative control. Organized mucosa-associated lymphoid tissue (MALT) is present in the nasolacrimal ducts displaying the cytomorphological and immunophenotypic features of MALT. CONCLUSIONS: The normally constant absorption of tear fluid components into the blood vessels of the surrounding cavernous body that are connected to the blood vessels of the outer eye, could be a feedback signal for tear fluid production, which comes to a halt if these tear components are not absorbed. Thus, dry eye could be initiated. Defective stimulation of tear duct-associated lymphoid tissue (TALT) could result in abnormal immune deviation at the ocular surface leading to an autoimmunological response that causes dry eye pathology.     

环孢素A滴眼液治疗结膜干燥综合征小鼠的机制

目的 探讨环孢素A滴眼液治疗结膜干燥综合征的治疗作用及治疗机制。方法 应用百日咳疫苗联合完全弗氏佐剂及同种鼠结膜抗原，多点注射小鼠诱导结膜干燥综合征动物模型。分别用0．05％或1％环孢素A滴眼液及0．025％地塞米松滴眼液予以治疗，并以注射0．9％氯化钠溶液小鼠作为对照组。观察对照组及各实验组治疗前后泪液分泌量、泪膜破裂时间的变化；作病理切片观察结膜杯状细胞破坏程度及破坏后的恢复程度，淋巴细胞浸润程度；用免疫组化SP法测量结膜上皮细胞和杯状细胞及腺样层水通道蛋白3（AQP3）表达量的变化。结果 0．05％环孢素A滴眼液治疗前后小鼠泪液分泌量、泪膜破裂时间、结膜杯状细胞数和AQP3表达量都有明显变化，淋巴细胞浸润程度减轻；1％环孢素A滴眼液虽然也有明显治疗作用，但对眼表有明显刺激；0．025％地塞米松滴眼液无明显治疗作用。结论 环孢素滴眼液对结膜干燥综合征有明显治疗作用，机制包括抑制淋巴细胞，增加结膜杯状细胞的数量，上调结膜上皮细胞和杯状细胞及腺样层AQP3的表达量。     

Mehrjahresverlauf nach Autotransplantation der Unterkieferspeicheldrüse bei vernarbender Keratokonjunktivitis mit absolutem Tränenmangel

ZusammenfassungZiel Eine Unterkieferspeicheldrüse kann durch Transplantation in die Schläfenregion zur Benetzung bei vernarbender Keratokonjunktivitis mit absolutem Tränenmangel genutzt werden. Wir berichten über unsere Erfahrungen mit diesem Verfahren.Patienten und Methoden In einer prospektiven, kontrollierten, klinischen Kohortenstudie untersuchten wir die Entwicklung von Schirmer-Test, Fluoreszein-Break-up-time, subjektiver Beschwerdesymptomatik, Verwendung von pharmazeutischen Tränenersatzmitteln, Visus, Bengalrosafärbung und Bindehauthyperämie bei 14 Augen mit vitalem Speicheldrüsentransplantat und 11 trockenen Augen ohne speichelartige Benetzung bei schwerster vernarbender KCS.Ergebnisse Über 3,3 Jahre postoperativ zeigte sich in der Transplantatgruppe gegenüber präoperativ und gegenüber der Kontrollgruppe eine signifikante Verbesserung des Beschwerdebildes bei gleichzeitig reduzierter Verwendung von Tränenersatzmitteln.Schlussfolgerung Bei extrem trockenem Auge kann die Transplantation einer autologen Unterkieferspeicheldrüse die Benetzung und die oft schwersten Beschwerden des Tränenmangels deutlich und langfristig verbessern. Das Verfahren eignet sich zur symptomatischen Therapie bei verzweifelten Fällen des absoluten Tränenmangels.     

Ocular surface lesions due to keratoconjunctivitis sicca: in primary Sjögren's syndrome

Keratoconjunctivitis sicca is usually part of Sjögren's syndrome (SS) which is systemic disease. Ocular surface lesions are ascribed either to the reduction, or to the low quality of tears. To address this question, ocular surface lesions were evaluated in 20 SS patients by the rose bengal test (RBT). The results were compared to those obtained in 20 normal volunteers and collated with the quality (estimated by the break-up-time) and the quantity of tears (estimated by the shirmer's I test and the level of lacrimal lactoferrin, LF). The RBT scores did not correlate with the shirmer's test results, neither did they with the break-up times. This is consistent with the view that Schirmer's I Test and break-up-time cannot make any distinction between patients from controls. In contrast, the RBT scores correlated well with the levels lacrimal LF and paralleled to serological abnormalities.