Ocular Pathophysiology of Sjögren's Syndrome.

The purpose of this review is to delve into the clinical and research understanding of the pathophysiology and presentation of Sjögren's-related keratoconjunctivitis sicca in order address the diagnostic and management challenge that it represents, as well as to provide a basis for appreciating the pharmacotherapies designed to treat the ophthalmic symptoms of Sjögren's disease.

Long-term Outcomes of Punctal Cauterization in the Management of Ocular Surface Diseases.

PURPOSE: To evaluate the long-term outcomes of surgical occlusion of lacrimal puncta using thermal cautery in the management of ocular surface diseases. METHODS: We reviewed medical records of 80 consecutive patients from a single academic center who underwent punctal cauterization. Patient demographics, ocular history, symptoms, and signs of ocular surface diseases pre- and post-cauterization were recorded. RESULTS: A total of 80 patients (171 puncta) were included, with an average age of 59 years and a follow-up duration of 27 months. The most common ocular morbidity was ocular graft-versus-host disease (n = 36), followed by primary keratoconjunctivitis sicca (n = 15). Indications for punctal cauterization included plug loss (n = 51), difficulty in plug fitting (n = 11), plug-related complications (n = 6), recanalization of previous cauterization (n = 7), and severe ocular surface disease requiring permanent punctal closure (n = 4). After punctal cauterization, the percentage of eyes with severe (21%) and moderate (25%) dry eye decreased significantly (8% and 19% at 3 months and 6% and 17% at 12 months, P = 0.0006). Fifty-four percent of patients reported improvement in their symptoms. The rate of recanalization was 21% during the follow-up period. The use of topical corticosteroids was associated with higher recanalization rate. Associated complications were limited to temporary pain and swelling. CONCLUSIONS: Punctal cauterization is an effective modality in treating severe ocular surface diseases in patients who repeatedly lose punctal plugs, and it can be easily performed in a clinic setting without major complications. However, cauterization may need to be repeated in up to a quarter of cases because of recanalization.

Clinical Profile in Genetically Proven Blau Syndrome: A Case Series from South India.

Purpose: To report the clinical profile of genetically proven Blau syndrome in seven cases from a single center in South India.Materials & Methods: Retrospective case seriesResults: There were four females and three males. All cases had a history of skin and joint involvement of varying severity. Flexion contractures of the proximal interphalangeal joints were seen in all cases except Case 2. Ocular involvement was bilateral and included keratoconjunctivitis sicca (six cases), granulomatous panuveitis (three cases), granulomatous anterior uveitis (three cases), conjunctival granulomas (three cases), subepithelial corneal opacities (one case), and subretinal granuloma (one case). Other ocular findings included band-shaped keratopathy (five cases) and cataract (three cases). All cases received oral steroids and methotrexate with an addition of mycophenolate mofetil in one case. Visual prognosis was good in all cases.Conclusions: Blau syndrome is underreported in India. This is the largest case series of genetically proven Blau syndrome from South India and highlights the clinical profile of Blau syndrome seen in India.

Clinical features and outcomes from the Singapore Sjögren's syndrome study.

OBJECTIVE: To study the clinical features, treatment and outcomes of primary Sjögren's Syndrome (pSS) in a Singapore cohort from an outpatient rheumatology clinic. METHODS: Computerised Physician Order entry records of patients who fulfilled the 2016 ACR-EULAR classification criteria for pSS between 1993 and 2013 were retrospectively analysed. RESULTS: There were 102 patients, of which 96 (94.1%) were females, and 91 (89.2%) Chinese. Mean age at diagnosis was 49.3 ± 11.8 years, mean disease duration was 9.0 ± 4.6 years. The most common manifestations were keratoconjunctivitis sicca (99.0%), xerostomia (96.1%), arthralgia/arthritis (56.9%). Exocrine glandular enlargement comprised parotidomegaly (28, 27.5%), with concurrent submandibular and lacrimal gland enlargement in one. The nervous system (15.7%) was the most commonly affected internal organ, with peripheral nervous system (peripheral neuropathy, mononeuritis multiplex) involvement more common than central. Hydroxychloroquine was most frequently used (88.2%), followed by methotrexate (7.8%) and azathioprine (6.9%). Pulsed intravenous (IV) methylprednisolone 500 mg/day for 3 days was used in 5 patients followed by oral (4) or IV cyclophosphamide (1) for cardiomyopathy and interstitial lung disease (1), and neurological involvement (4). These comprised neuromyelitis optica, transverse myelopathy, cranial neuropathy, mononeuritis multiplex and/or peripheral neuropathy alone or in combination. Intravenous immunoglobulins (2.0%) was used for sensory neuropathy and mononeuritis multiplex; rituximab (1.0%) in 1 patient for treatment of non-Hodgkin's B-cell lymphoma. There were no deaths. CONCLUSION: Musculoskeletal manifestations were common, with the nervous system (peripheral more than central) the most common internal organ involved. Lymphoma was uncommon despite up to one-third of the cohort developing glandular enlargement.

Nuclear parameters and chromatin remodeling in epithelial cells and lymphocytes from the palpebral conjunctiva of dogs with keratoconjunctivitis sicca.

OBJECTIVE: To study parameters related to nuclear morphology and chromatin remodeling in epithelial cells and lymphocytes from the inferior palpebral conjunctiva of dogs with and without keratoconjunctivitis sicca (KCS). ANIMALS STUDIED: Thirty-two dogs (64 eyes) were included in the study. Based on the tear production measured by Schirmer tear test 1, the dogs were distributed into control and KCS groups. PROCEDURES: Epithelial cells and lymphocytes were collected by conjunctival brush cytology, fixed on glass slides, and subjected to the Feulgen reaction, a topochemical method specific for DNA/chromatin. Feulgen-stained cells were studied by microscopy and video image analysis to establish nuclear size (area and perimeter) and shape (relative nuclear roundness factor = RNRF), DNA content (ploidy), and compaction and texture of chromatin. RESULTS: Conjunctival samples in the KCS group showed infiltration of inflammatory and immune cells. Micronuclei, snake-like chromatin, aberrant chromosomes, and goblet cells were not detected. Compared with the controls, cells on the conjunctival surface of dogs with KCS showed altered nuclei. Conjunctival epithelial cells were more affected by KCS (changes in nuclear size, shape, DNA content, and chromatin compaction) than lymphocytes (changes in chromatin compaction, only). Significant chromatin decompaction was observed in both conjunctival epithelial cells and lymphocytes. CONCLUSIONS: Our results show that KCS promotes chromatin remodeling in epithelial cells and lymphocytes on the conjunctival surface of dogs. The changes described in this study are different from those reported for conjunctival cell nuclei of human KCS patients.

[New approaches to the treatment of keratoconjunctivitis sicca]. / Novye podkhody k lecheniiu sukhogo keratokon''iunktivita.

A new method has been developed for the treatment of severe forms of keratoconjunctivitis sicca (KCS) that involves the use of an original cyclosporine A (CyA) saturated soft contact lens (SCL) together with preservative-free artificial tears therapy. AIM: to evaluate the effectiveness of the newly developed treatment for KCS based on the use of medical SCL saturated with 0.05% CyA. MATERIAL AND METHODS: The patients (43 men, 60 eyes) with severe KCS were divided into 2 groups. Group 1 included 21 patients (30 eyes), who received artificial tears and wore 0.05% CyA-saturated silicone-hydrogel SCLs. Group 2 included 22 patients (30 eyes), who wore unsaturated original SCLs and received CyA instillations 2 times daily and, also, artificial tears. Apart from a standard ophthalmic examination, the assessment included Schirmer's test, Norn's test, vital eye stain tests, tear osmometry, laser confocal tomography of the cornea, optical coherence tomography of the anterior segment with meniscometry, impression cytology of the conjunctiva, tear pH measurement, plating of the content of the conjunctival cavity, measurement of the width of the palpebral fissure, and calculation of the ocular surface disease index. Treatment results were followed up at 1, 3, 6, and 12 months. RESULTS: The use of 0.05% CyA-saturated SCLs allows to halve treatment time for patients with severe KSC (down to 1 week - 1 month) as compared to unsaturated original SCLs in combination with 0.05% CyA instillations and to reduce it 5 times as compared to 0.05% CyA instillations only. CONCLUSION: The new method of KSC treatment that involves the use of medical SCL of original design (ensures even distribution of 0.05% CyA across the ocular surface) and preservative-free artificial tears has demonstrated high therapeutic effectiveness as compared to existing methods.

The Effect of Ocular Surface Regularity on Contrast Sensitivity and Straylight in Dry Eye.

Purpose: To investigate the association between visual function and ocular surface regularity in dry eye. Methods: We enrolled 52 eyes of 52 dry eye patients (34 dry eyes with superficial punctate keratopathy [SPK] in the central corneal region [central SPK] and 18 dry eyes without central SPK) and 20 eyes of 20 normal control subjects. All eyes had a best-corrected distance visual acuity better than 20/20. We measured two indices of contrast sensitivity function under photopic conditions: contrast sensitivity and letter contrast sensitivity. The area under the log contrast sensitivity function (AULCSF) was calculated from the obtained contrast sensitivity data. Straylight was quantified using a straylight meter. Results: Dry eyes with central SPK had significantly decreased contrast sensitivity function, including AULCSF and letter contrast sensitivity than those without central SPK and normal eyes (P < 0.05 for each). While the straylight values in both dry eye groups did not differ, straylight values were greater than those in normal eyes (P < 0.05 for both). In dry eye, the AULCSF and letter contrast sensitivity negatively correlated with the central SPK score (R = -0.485, P < 0.001, and R = -0.541, P < 0.001, respectively). Conclusions: In dry eye, reduced contrast sensitivity in part results from central SPK overlying the optical zone and the increased straylight results from tear film instability rather than central SPK.

Dysfunctional tear syndrome: dry eye disease and associated tear film disorders - new strategies for diagnosis and treatment.

Dysfunctional tear syndrome (DTS) is a common and complex condition affecting the ocular surface. The health and normal functioning of the ocular surface is dependent on a stable and sufficient tear film. Clinician awareness of conditions affecting the ocular surface has increased in recent years because of expanded research and the publication of diagnosis and treatment guidelines pertaining to disorders resulting in DTS, including the Delphi panel treatment recommendations for DTS (2006), the International Dry Eye Workshop (DEWS) (2007), the Meibomian Gland Dysfunction (MGD) Workshop (2011), and the updated Preferred Practice Pattern guidelines from the American Academy of Ophthalmology pertaining to dry eye and blepharitis (2013). Since the publication of the existing guidelines, new diagnostic techniques and treatment options that provide an opportunity for better management of patients have become available. Clinicians are now able to access a wealth of information that can help them obtain a differential diagnosis and treatment approach for patients presenting with DTS. This review provides a practical and directed approach to the diagnosis and treatment of patients with DTS, emphasizing treatment that is tailored to the specific disease subtype as well as the severity of the condition.

Ageing and ocular surface immunity.

The prevalence of ocular surface immunopathologies is enhanced in the elderly. This increased prevalence has been attributed to age-related dysregulation of innate and adaptive immune system responses. Age-related changes in ocular surface immunity have similar and distinct characteristics to those changes seen in other mucosal tissues. This mini review provides a brief outline of key findings in the field of ocular ageing, draws comparisons with other mucosal tissues and, finally, discusses age-related changes in the context of immunopathogenesis of infectious keratitis and dry eye disease, two of the most common inflammatory disorders of the ocular surface.

[Effectiveness of soft contact lenses in severe keratoconjunctivitis sicca treated with local immunosuppressive therapy]. / Effektivnost' lechebnykh myagkikh kontaktnykh linz pri immunosupressivnoi terapii sukhogo keratokon''yunktivita.

AIM: To study the effectiveness of soft contact lenses in severe keratoconjunctivitis sicca (KCS) treated with local immunosuppressive therapy. MATERIAL AND METHODS: We have examined 41 patients (60 eyes) with severe KCS, including 3 men (4 eyes) and 38 women (56 eyes) aged from 27 to 76 years. Group 1 consisted of 22 persons (30 eyes) who were prescribed cyclosporine А 0.05% instillations 2 times daily, artificial tears, and soft contact lenses. Group 2 consisted of 19 patients (30 eyes) who received instillations of cyclosporine А 0.05% 2 times daily for no less than 6 months and artificial tears. Apart from the standard ophthalmic examination, the assessment included Schirmer's test, tear break-up time test, fluorescein eye stain test, tear osmometry, Heidelberg tomography of the cornea, optical coherence tomography of the anterior segment with meniscometry, impression cytology of the conjunctiva, tear pH measurement, plating of the content of the conjunctival cavity for its microflora, measurement of the width of the palpebral fissure, and calculation of the ocular surface disease index (OSDI). Treatment outcomes were evaluated at 1, 3, 6, and 12 months. RESULTS: In group 1, complete re-epithelialization of the cornea (confirmed by all the methods used) was achieved rather shortly, in 1-3 months, while in group 2 - in 6 months. CONCLUSION: The use of soft contact lenses in addition to cyclosporine A instillation therapy promotes restoration of corneal and conjunctival epithelium, reduces treatment time, and improves quality of life for patients, thus, proving itself a safe and effective treatment of autoimmune KCS.

Dry Eye Disease: Present Challenges in the Management and Future Trends.

Dry eye disease (DED) is a tear film disorder resulting in hyperosmolarity of the tear film and inflammation of the ocular surface. DED is also referred to as keratoconjunctivitis sicca (KCS) and dry eye syndrome. DED represents a significant public health issue, particularly in older adults, and needs more research and attention. Despite the urgent need for safe and effective pharmacotherapies, there is currently only one approved medication, Restasis®, to tackle DED. In this review article, we present an overview of DED, classification, epidemiology, pathophysiology, diagnosis, and risk factors of DED. Special emphasis is placed on current treatment options for DED such as artificial tears, lipid-containing lubricants, liposomal spray, inserts, anti-inflammatory or immunosuppressant drops, antibiotics, dietary omega-3 essential fatty acids, autologous serum, intense-pulsed-light (IPL), punctual plugs, moisture-retaining eyeglasses, hydrophilic bandage contact lenses and secretagogues. The review also summarizes trends in DED treatment that are patented and are currently under investigation in clinical trials.

[Significance of laser confocal tomography in diagnosis and monitoring of keratoconjunctivitis sicca].

UNLABELLED: Laser confocal tomography of the cornea enables studying ultrathin sections of corneal layers, which provides additional reliable information on tissue changes in keratoconjunctivitis sicca (KCS). AIM: To assess the significance of laser confocal tomography of the cornea in the diagnosis and monitoring of KCS. MATERIAL AND METHODS: We investigated 38 eyes of 30 patients with severe KCS. The patients were divided into two groups. Group 1 (15 patients, 19 eyes) was prescribed cyclosporine А 0.05% instillations 2 times daily, artificial tears, and soft contact lenses. Group 2 (15 patients, 19 eyes) received only instillations of cyclosporine А 0.05% 2 times daily and artificial tears. Besides standard ophthalmic examination, additional tests were performed, namely Schirmer's test, tear break-up time test, fluorescein eye stain test, tear osmolarity test (TearLab System, USA), and Heidelberg retinal tomography of the cornea (HRT, Heidelberg Engineering GmbH, Germany). RESULTS: HRT findings revealed a 3 times shorter epithelization period and faster recovery of corneal transparency in group 1 as compared to group 2 (1.5 and 4.5 months, respectively). There was also an evident reduction in the number of immune cells in the cornea, most pronounced in group 1 at 3 months, which is indicative of inflammation termination. CONCLUSION: The use of HRT of the cornea in KCS patients allows real-time cellular level observation of corneal changes, which together with clinical findings and diagnostic tests not only confirms the diagnosis but also determines treatment effectiveness. It has been also found that soft contact lenses accelerate epithelization of the cornea and relieve inflammation of the ocular surface in KCS patients under cyclosporine A 0.05% instillation therapy. Transparency of financial activity: the authors have no financial interest in the submitted materials and methods.

Increased Straylight in Patients With Keratoconjunctivitis Sicca.

PURPOSE: (1) To qualify complaints of quality of vision in patients with (severe) keratoconjunctivitis sicca by examining straylight values and (2) to check for an effect of scleral lens wear on straylight. METHODS: Straylight was measured in 16 patients with severe keratoconjunctivitis sicca using the Oculus C-Quant. In 9 of these patients, scleral lenses were used, and straylight was measured with and without scleral lenses. Other tests included the Schirmer test, visual acuity, the van Bijsterveld score, and a straylight questionnaire. RESULTS: Patients with keratoconjunctivitis sicca had a mean straylight OD of log(s) = 1.36 ± 0.19 SD and OS of log(s) = 1.45 ± 0.17 SD. Mean age was 56 ± 9.3 SD. This was significantly higher than the mean age-matched normal value of log(s) = 1.10 (P < 0.001). Such a straylight increase is functionally significant. The difference in straylight with and without scleral lenses was 0.06 log units ± 0.02 SD, but this was not statistically significant for OD (P = 0.134) and OS (P = 0.293). No correlation was found between straylight and the van Bijsterveld score on the corneal section for OD (P = 0.326) and OS (P = 0.433). CONCLUSIONS: Keratoconjunctivitis sicca leads to increased straylight. However, this increase was not correlated to the amount of surface damage graded with the van Bijsterveld score. Further study on the cornea is necessary to determine the source of the increased straylight. Scleral lenses do not have a noteworthy influence on straylight in these patients.

Ophthalmic manifestations of perinatally acquired HIV in a US cohort of long-term survivors.

BACKGROUND/AIMS: To determine the ophthalmic manifestations of HIV in a cohort of long-term survivors of perinatally acquired HIV. METHODS: Twenty-two patients with perinatally acquired HIV who were aged ≥12 years were prospectively studied at a university clinic. They underwent complete ophthalmic examinations and fundus photography. Their medical histories, medications and CD4 counts were abstracted from the medical records. To evaluate for keratoconjunctivitis sicca, both HIV patients and 44 healthy controls (matched by age, gender and contact lens wear) underwent Schirmer testing and ocular surface staining. RESULTS: Nine male and 13 female HIV patients with mean age of 16.6 years (SD, 3.4) were examined. Of the 22 HIV patients, 21 had been treated with highly active antiretroviral therapy (HAART). Only one patient had a CD4 count nadir of <200 cells/µL. The mean visual acuity of the eyes of the HIV subjects was 20/22 (SD, 1.6 lines). No patient had cytomegalovirus retinitis. Four of the 22 (18%) HIV patients had strabismus. HIV subjects and controls had similar rates of abnormal Schirmer (9% and 14%, p=0.62) and ocular staining scores (p=0.29). CONCLUSIONS: In the post-HAART era, long-term survivors of perinatally acquired HIV exhibited little vision-threatening disease, but had a high prevalence of strabismus.

Infrared ocular thermography in dogs with and without keratoconjunctivitis sicca.

Infrared thermography was used to measure temperature differences of the corneal surface between nasal and temporal limbus regions and central cornea of normal dogs and dogs with keratoconjunctivitis sicca (KCS), in order to establish temperature values in normal canine eyes and in patients with decreased Schirmer tear tests (STT) values. Dogs investigated were all either patients seen at the Veterinary Teaching Hospital of Federal University of Paraná or normal dogs that belonged to the same institution. STT were performed in all eyes. A total of 40 control eyes (STT ≥15 mm/min) and 20 eyes with low STT values (STT ≤14 mm/min) were examined. The mean STT value for eyes with normal STT values was 22.9 ± 3.9 mm/min (mean ± standard deviation), and the mean STT value for eyes with low STT value was 7.2 ± 4.8 mm/min. The mean corneal temperature was significantly lower in eyes with low STT values than in control eyes (P < 0.0001). The following significant correlations were found: (i) Schirmer and breakup time (BUT) (P = 0.0001, r = 0.5); (ii) STT values and corneal surface temperature (P = 0.001, r = 0.256); (iii) STT values and age (P = 0.0001, r = -0.448); (iv) age and corneal surface temperature (P = 0.0001, r = -0.281); and (v) BUT and corneal surface temperature (P = 0.0001, r = 0.36). Thermography is a method that can differentiate between eyes with normal and abnormal STT values. In the future, thermography might be incorporated as part of the ophthalmic examination and perhaps become a popular ancillary test for the diagnoses of ocular surface disorders.

Effect of diquafosol ophthalmic solution on the optical quality of the eyes in patients with aqueous-deficient dry eye.

PURPOSE: To investigate the short- and long-term effects of diquafosol ophthalmic solution on the optical quality of the eyes in patients with aqueous-deficient dry eye. METHODS: Sixteen eyes in 16 patients with mild or moderate aqueous-deficient dry eye were treated with 3% diquafosol ophthalmic solution. Ocular higher-order aberrations (HOAs) were measured with a wavefront sensor before and at 15 min after diquafosol instillation at the baseline visit and at 4 weeks after treatment initiation. Dry eye symptoms, tear break-up time (BUT), corneal/conjunctival fluorescein staining and Schirmer's test were also evaluated before and after treatment with diquafosol. RESULTS: Treatment with diquafosol ophthalmic solution significantly improved dry eye symptoms, corneal staining and BUT. Compared with mean total HOAs at baseline (0.180 ± 0.06 µm), those at 4 weeks after treatment significantly decreased (0.148 ± 0.039 µm; p = 0.035), whereas those 15 min after diquafosol instillation at the baseline visit did not change significantly (0.170 ± 0.049 µm; p = 0.279). CONCLUSIONS: Although no significant change in HOAs was observed as a short-term effect of a single-drop instillation of diquafosol, long-term use of diquafosol to treat aqueous-deficient dry eye reduced HOAs as well as improved corneal epithelial damage and tear film stability.

Rethinking dry eye disease: a perspective on clinical implications.

Publication of the DEWS report in 2007 established the state of the science of dry eye disease (DED). Since that time, new evidence suggests that a rethinking of traditional concepts of dry eye disease is in order. Specifically, new evidence on the epidemiology of the disease, as well as strategies for diagnosis, have changed the understanding of DED, which is a heterogeneous disease associated with considerable variability in presentation. These advances, along with implications for clinical care, are summarized herein. The most widely used signs of DED are poorly correlated with each other and with symptoms. While symptoms are thought to be characteristic of DED, recent studies have shown that less than 60% of subjects with other objective evidence of DED are symptomatic. Thus the use of symptoms alone in diagnosis will likely result in missing a significant percentage of DED patients, particularly with early/mild disease. This could have considerable impact in patients undergoing cataract or refractive surgery as patients with DED have less than optimal visual results. The most widely used objective signs for diagnosing DED all show greater variability between eyes and in the same eye over time compared with normal subjects. This variability is thought to be a manifestation of tear film instability which results in rapid breakup of the tearfilm between blinks and is an identifier of patients with DED. This feature emphasizes the bilateral nature of the disease in most subjects not suffering from unilateral lid or other unilateral destabilizing surface disorders. Instability of the composition of the tears also occurs in dry eye disease and shows the same variance between eyes. Finally, elevated tear osmolarity has been reported to be a global marker (present in both subtypes of the disease- aqueous-deficient dry eye and evaporative dry eye). Clinically, osmolarity has been shown to be the best single metric for diagnosis of DED and is directly related to increasing severity of disease. Clinical examination and other assessments differentiate which subtype of disease is present. With effective treatment, the tear osmolarity returns to normal, and its variability between eyes and with time disappears. Other promising markers include objective measures of visual deficits, proinflammatory molecular markers and other molecular markers, specific to each disease subtype, and panels of tear proteins. As yet, however, no single protein or panel of markers has been shown to discriminate between the major forms of DED. With the advent of new tests and technology, improved endpoints for clinical trials may be established, which in turn may allow new therapeutic agents to emerge in the foreseeable future. Accurate recognition of disease is now possible and successful management of DED appears to be within our grasp, for a majority of our patients.

New therapies in common ocular surface disorders.

Lacrimal dysfunction syndrome (LDS) and meibomian gland dysfunction (MGD) are common pathologies of the ocular surface both characterized by quantitative and/or qualitative tear film changings. They may result in symptoms of eye irritation, clinically apparent inflammation and ocular surface disease. Recent researches about the chronic inflammatory nature of dry eye, revealed the possibility to develop new treatments for LDS like new immunological drugs. MGD, alone or if it occurs contemporary to LDS, can be treated with a thermal pulsation system, a useful tool to alleviate symptoms.

Punctal plugs versus artificial tears for treating primary Sjögren's syndrome with keratoconjunctivitis SICCA: a comparative observation of their effects on visual function.

To compare the effects of treatment with punctal plugs versus artificial tears on visual function for primary Sjögren's syndrome with dry eye. Forty-two eyes of 42 patients with primary Sjögren's syndrome were enrolled and were allocated randomly into artificial tears (AT) group and punctal plugs (PP) group. Ocular Surface Disease Index (OSDI) was used, and fluorescent staining for tear film break-up time (BUT), the Schirmer test I (STI) and contrast sensitivity was performed before treatment and was repeated 3 months after treatment. A follow-up of 3 months was achieved in 40 eyes of 40 patients, including 19 eyes in artificial tears group and 21 eyes in punctal plugs group. Statistically significant improvements were observed in the OSDI scores (AT: 52.6 ± 5.7, 15.9 ± 4.2; PP: 55.8 ± 4.9, 15.1 ± 4.2), corneal fluorescein staining scores (AT: 2.60 ± 1.76, 0.30 ± 0.57; PP: 1.91 ± 1.60, 0.09 ± 0.29), STI (AT: 3.85 ± 2.03, 8.95 ± 2.72; PP: 3.36 ± 1.62, 11.41 ± 2.65), and BUT (AT: 2.60 ± 1.39, 6.00 ± 1.81; PP: 2.27 ± 1.12, 7.82 ± 1.84) after treatment compared to those of pre-treatment. The values of STI (AT: 5.10 ± 1.80; PP: 8.05 ± 1.53) and BUT (AT: 3.40 ± 1.31; PP: 5.68 ± 1.13) in punctal plugs group were significantly more improved than those in the artificial tears group. The medium- and high-level frequencies contrast sensitivities were greatly improved in simulated daylight, night, and glare disability conditions after treatment with artificial tears and punctal plugs. However, the changes in contrast sensitivity did not significantly differ between groups. Both artificial tears and punctal plugs relieved dry eye symptoms, repaired corneal lesions, enhanced tear film stability, and improved contrast sensitivity. Punctal plugs could improve tear film stability and elongate the BUT better than artificial tears.

Primary Sjögren syndrome: an update on current pharmacotherapy options and future directions.

INTRODUCTION: Primary Sjögren syndrome (SS) is a chronic systemic autoimmune disease characterized by sicca features and systemic manifestations, and requires a multidisciplinary therapeutic approach. AREAS COVERED: Treatment of sicca manifestations is symptomatic and is based on the administration of topical therapies (saliva substitutes and preservative-free artificial tears). In severe cases of keratoconjunctivitis sicca, topical cyclosporine A may be used. For patients with residual salivary gland function, stimulation of salivary flow with a sialogogue (pilocarpine or cevimeline) is the treatment of choice. The management of extraglandular features must be tailored to the specific organ(s) involved. Hydroxychloroquine may be appropriate for patients with fatigue, arthralgia and myalgia, while glucocorticoids and immunosuppressive agents should be reserved for severe systemic involvement (although no controlled trials in primary SS guide their use). RCTs have demonstrated the lack of efficacy of antitumor necrosis factor agents and promising results for B-cell depleting agents. EXPERT OPINION: The overall low level of evidence in therapeutic studies in primary SS suggests that much larger trials of the most promising therapies are necessary. The use of drugs targeting molecules and receptors involved in the etiopathogenesis of primary SS may open up a new era in the therapeutic management of the disease, but the potential risks and benefits of these agents must be weighed carefully.