Enduring remission of active and sight-threatening Graves' orbitopathy with rituximab: report of two cases.

Intravenous (i.v.) glucocorticosteroids (GCs) constitute the first-line treatment for active and moderate-to-severe Graves' orbitopathy (GO). In cases of persistent disease, rituximab, a monoclonal anti-CD20 antibody, may be used, although studies have yielded conflicting results. In case 1, a 50-year-old female heavy smoker presented with severe bilateral disfiguring eyelid edema of four months, bilateral exophthalmos and a clinical activity score (CAS) of 5/7. Laboratory investigation showed thyrotoxicosis and high thyroid-stimulating immunoglobulin (TSI) levels [32 IU/L (normal <1.75]. After minor improvement by i.v. methylprednisolone and standard retrobulbar radiotherapy (20 Gy), her visual acuity progressively declined to "hand motion". Rituximab was administered (two pulses of 500 mg, two weeks apart), with significant response. At 3 1/2 years of follow-up, CAS is 0/7 and CD20+ lymphocytes remain at the lower normal range. In case 2, a 78-year-old non-smoker male was referred for management of severe active GO, one month after total thyroidectomy for Graves' thyrotoxicosis (TSI: 6.74 IU/L). Over the preceding two-three months, severe GO manifested with chemosis, constant diplopia, loss of color vision and acuity of 1/10 bilaterally (CAS: 7/7). Following partial response to i.v. methylprednisolone and concomitant radiotherapy, rituximab (two pulses of 500 mg each, two weeks apart), was administered. Vision partially recovered and GO remains in remission one year later, even after 131I (100 mCi) administration for papillary thyroid carcinoma (TSI: 0.9 IU/L and CD20+ count at the lower normal range). In conclusion, rituximab may be an effective second-line therapy in GO patients, providing long-lasting remission.

Selenium and the course of mild Graves' orbitopathy.

BACKGROUND: Oxygen free radicals and cytokines play a pathogenic role in Graves' orbitopathy. METHODS: We carried out a randomized, double-blind, placebo-controlled trial to determine the effect of selenium (an antioxidant agent) or pentoxifylline (an antiinflammatory agent) in 159 patients with mild Graves' orbitopathy. The patients were given selenium (100 µg twice daily), pentoxifylline (600 mg twice daily), or placebo (twice daily) orally for 6 months and were then followed for 6 months after treatment was withdrawn. Primary outcomes at 6 months were evaluated by means of an overall ophthalmic assessment, conducted by an ophthalmologist who was unaware of the treatment assignments, and a Graves' orbitopathy-specific quality-of-life questionnaire, completed by the patient. Secondary outcomes were evaluated with the use of a Clinical Activity Score and a diplopia score. RESULTS: At the 6-month evaluation, treatment with selenium, but not with pentoxifylline, was associated with an improved quality of life (P<0.001) and less eye involvement (P=0.01) and slowed the progression of Graves' orbitopathy (P=0.01), as compared with placebo. The Clinical Activity Score decreased in all groups, but the change was significantly greater in the selenium-treated patients. Exploratory evaluations at 12 months confirmed the results seen at 6 months. Two patients assigned to placebo and one assigned to pentoxifylline required immunosuppressive therapy for deterioration in their condition. No adverse events were evident with selenium, whereas pentoxifylline was associated with frequent gastrointestinal problems. CONCLUSIONS: Selenium administration significantly improved quality of life, reduced ocular involvement, and slowed progression of the disease in patients with mild Graves' orbitopathy. (Funded by the University of Pisa and the Italian Ministry for Education, University and Research; EUGOGO Netherlands Trial Register number, NTR524.).

Impact of Light Conditions on Visual Performance following Premium Pseudophakic Presbyopia Corrections.

The primary objective of this study was to objectively compare the visual performance of patients following premium pseudophakic presbyopia corrections in different light combinations for near- and intermediate-vision activities of daily living (ADLs). This is a prospective, comparative study. A total of 75 patients populated three study groups: G1-patients with bilateral trifocal implantation, G2-patients with bilateral bifocal implantation, and G3-patients with bilateral monofocal implantation. All participants addressed 10 ADLs in nine combinations of light temperature (3000 K, 4000 K, and 6000 K) and light intensity (25 fc, 50 fc, and 75 fc) and declared their subjectively optimal light combination while reading. G2 and G3 had the best total ADL scores in 6000 K/75 fc, while G1 had the best total ADL score in 4000 K/75 fc. Total ADL, easy ADL, and moderate difficulty ADL scores were significantly better in G2, while difficult ADL score was significantly better in G1. The majority of all groups selected 6000 K/75 fc as the most comfortable light combination, and no group selected 3000 K and 25 fc. In conclusion, trifocal patients benefit from intense daylight, while bifocal and monofocal patients benefit from intense, cold lighting. Trifocal patients present superior near-vision capacity in difficult near-vision daily tasks, while bifocal patients present superiority in easy and moderate-difficulty ADLs.

Validation of a web-based distance visual acuity test.

PURPOSE: To validate the Democritus Digital Acuity and Reading Test (DDART) as a distance VA (dVA) test against a series of prevalent conventional distance vision charts. SETTING: Ophthalmology Department, University Hospital of Alexandroupolis, Alexandroupolis, Greece; Ophthalmology Department, AHEPA University Hospital, Thessaloniki, Greece; and Ophthalmica Institute of Ophthalmology & Microsurgery, Thessaloniki, Greece. DESIGN: Prospective multicenter validation study. METHODS: The distance best spectacle-corrected visual acuity (dBSCVA) was compared in normal (NVG) and low (LVG) vision participants against 4 prevalent conventional distance vision charts (ETDRS, Snellen, Landolt C, and Tumbling E) by a predefined 2.5-symbol noninferiority margin and intraclass correlation coefficients (ICCs). DDART's test-retest (TRT) reliability was assessed with ICCs. RESULTS: 534 participants (471 and 63 with normal and low vision, respectively) were included in the study. The mean difference between dBSCVA measured with DDART and conventional charts ranged between -0.84 and +0.85 symbols, without exceeding the 2.5-symbol noninferiority margin. ICCs indicated an excellent level of agreement for all patient groups (from 0.848 to 0.985). TRT reliability indicated differences below 1 symbol both for the NVG and LVG, with ICCs ranging between 0.912 and 0.964 for the 4 DDARTs. CONCLUSIONS: DDART was a valid web-based dVA test that provided reliable measurements in clinical and telemedical settings, both for normal and low vision patients.

Patient-reported burden and overall impact of dry eye disease across eight European countries: a cross-sectional web-based survey.

OBJECTIVE: Dry eye disease (DED) is a multifactorial disease involving the tears and ocular surface. It impacts a patient's quality of life (QoL) and ability to perform daily activities. This study assessed the burden of self-reported DED among adults in eight European countries. DESIGN: Online cross-sectional survey. SETTING: General population in France, Italy, Germany, Greece, the Netherlands, Portugal, Spain and Sweden. PARTICIPANTS: Adults aged ≥18 years with (n=6084) and without (n=6161) self-reported DED were recruited via emails and screened. MAIN OUTCOME MEASURES: All participants completed National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) and EuroQol-5 Dimension-5 Level Questionnaire (EQ-5D-5L). All DED participants completed the Eye Dryness Score (EDS) Visual Analogue Scale, and Ocular Comfort Index and Work Productivity and Activity Impairment Questionnaire: Specific Health Problem questionnaires. In addition, half of the respondents with DED completed Survey A (Impact of Dry Eye on Everyday Life) and the other half completed Survey B (Standard Patient Evaluation of Eye Dryness Questionnaire) and Dry Eye Questionnaire-5. RESULTS: Participants with self-reported DED had lower functional vision and lower overall health status than participants without self-reported DED as measured by the NEI-VFQ and EQ-5D-5L, respectively.Increasing self-reported DED severity as measured by the EDS was shown to correspond with worse symptom severity/frequency, lower functional vision, higher impact on work productivity, daily activities and QoL. CONCLUSION: This study showed that patients' reported burden of self-reported DED was similar across the eight European countries. Those with self-reported DED reported lower health status and functional vision compared to those without self-reported DED and these parameters worsen with increasing disease severity.

Interventions for involutional lower lid entropion.

BACKGROUND: Entropion is a condition in which the eyelid margin turns in against the eyeball. Involutional or senile entropion is one of the most common lower lid malpositions in the elderly. The interventions described and currently used for the treatment of this condition are surgical in nature, although non-surgical temporary medical treatment for the early stages of entropion has also been reported. The relative effectiveness of these interventions has not yet been resolved. OBJECTIVES: To examine the effect of interventions for involutional entropion and to assess whether any method is superior to any other. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 10), MEDLINE (January 1950 to November 2011), EMBASE (January 1980 to November 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com),ClinicalTrials.gov (http://clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 2 November 2011. We also searched oculoplastic textbooks, conference proceedings from the European and American Society of Ophthalmic Plastic and Reconstructive Surgery (ESOPRS, ASOPRS), European Ophthalmological Society (SOE), the Association for Recearch in Vision and Ophthalmology (ARVO) and American Academy of Ophthalmology (AAO) for the years 2000 to 2009 to identify relevant data. We attempted to contact researchers who are active in this field for information about further published or unpublished studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with no restriction on date or language comparing two or more surgical methods for correction of involutional lower eyelid entropion in people older than 60 years of age with involutional lower lid entropion. DATA COLLECTION AND ANALYSIS: Each review author independently assessed study abstracts identified from the electronic and manual searches. Author analysis was then compared and full papers for appropriate studies were obtained according to the inclusion criteria. Disagreements between the authors were resolved by discussion. MAIN RESULTS: We identified one RCT which met our inclusion criteria and was included in this review. Sixty-three participants with primary involutional lower eyelid entropion were randomised to everting sutures alone or everting sutures with a lateral tarsal strip. Eight participants were lost to follow-up. The trial indicates that the combined procedure for horizontal and vertical eyelid tightening in the form of everting sutures and lateral tarsal strip is highly curative for involutional entropion compared to vertical tightening in the form of everting sutures alone. The superiority of the combined approach is also supported by many good quality uncontrolled studies on specific surgical procedures but these were not included in the analysis as they were not part of the inclusion criteria. AUTHORS' CONCLUSIONS: A single RCT showed that the combination of horizontal and vertical eyelid tightening with everting sutures and lateral tarsal strip is highly efficient for entropion compared to vertical tightening with everting sutures alone. Retrospective case series studies also support the combined surgical repair but details from these studies on specific surgical techniques cannot be included in the analysis.Evidence from a single RCT is unlikely to change clinical practice and thus it is still our view that there is a clear need for more randomised studies comparing two or more surgical techniques for entropion surgery addressing the recurrence and complications rate.

Surgical orbital decompression for thyroid eye disease.

BACKGROUND: Orbital decompression is an established procedure for the management of exophthalmos and visual rehabilitation from optic neuropathy in cases of thyroid eye disease. Numerous procedures for removal of orbital bony wall, fat or a combination of these for a variety of indications in different stages of the disease have been well reported in the medical literature. However, the relative effectiveness and safety of these procedures in relation to the various indications remains unclear. OBJECTIVES: To review current published evidence for the effectiveness of surgical orbital decompression for disfiguring proptosis in adult thyroid eye disease and summa rise information on possible complications and the quality of life from the studies identified. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 10), MEDLINE (January 1950 to October 2011), EMBASE (January 1980 to October 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) and ClinicalTrials.gov (http://clinicaltrials.gov). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 6 October 2011. We searched oculoplastic textbooks, conference proceedings from the European and American Society of Ophthalmic Plastic and Reconstructive Surgery (ESOPRS, ASOPRS), European Ophthalmological Society (SOE), the Association for Research in Vision and Ophthalmology (ARVO) and American Academy of Ophthalmology (AAO) for the years 2000 to 2009 to identify relevant data. We attempted to contact researchers who are active in this field for information about further published or unpublished studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with no restriction on date or language comparing two or more surgical methods for orbital decompression with removal of bony wall, orbital fat or a combination of both for disfiguring proptosis or comparison of surgical techniques with any form of medical decompression. DATA COLLECTION AND ANALYSIS: Each review author independently assessed study abstracts identified from the electronic and manual searches. Author analysis was then compared and full papers for appropriate studies were obtained according to the inclusion criteria. Disagreements between the authors were resolved by discussion. MAIN RESULTS: We identified two randomised trials eligible for inclusion in the review. There was significant variability between the trials for interventions, methodology and outcome measures and therefore meta-analysis was not performed. One study suggested that the transantral approach and endoscopic transnasal technique had similar effects in reducing exophthalmos but that the endoscopic approach may be safer, relating to fewer complications. This study had short-term follow-up and lacked information on our primary outcome (success or failure of treatment). The second study provided evidence that intravenous steroids may be superior to primary surgical decompression in the management of compressive optic neuropathy requiring less secondary surgical procedures, although it relates more frequently to transient side effects. This study was weakened by a small sample size. Until more credible evidence is available recommendations as to best treatment cannot be reliably made. AUTHORS' CONCLUSIONS: A single study showed that the transantral approach for orbital decompression was related to more complications than the endoscopic transnasal technique which is preferred by Ear, Nose and Throat (ENT) surgeons, usually as an adjunctive procedure. Intravenous steroids were reported in a single trial to be the most efficient intervention for dysthyroid optic neuropathy. The majority of published literature on orbital decompression for thyroid eye disease consists of retrospective, cohort, or case series studies. Although these provide useful descriptive information, clarification is required to show the relative effectiveness of each intervention for various indications.The two RCTs reviewed are not robust enough to provide credible evidence to our understanding of current decompressive surgery and to support recommendations for clinical practice. There is evidence from currently available uncontrolled studies that removal of the medial and lateral wall (balanced decompression) with or without fat removal may be the most effective surgical method related to only a few complications.There is a clear need for randomised studies evaluating the balanced two-wall, three-wall and orbital fat decompression techniques. Comparison with other surgical techniques for orbital decompression or with immunosuppression in cases of compressive optic neuropathy would also be important. These studies should primarily address the reduction of exophthalmos, disease severity, complication rates, quality of life and cost of the intervention.

Hypopyon after Primary Cryopreserved Amniotic Membrane Transplantation for Sterile Corneal Ulceration: A Case Report and Review of the Literature.

Purpose. To report the acute development of hypopyon after primary cryopreserved amniotic membrane transplantation (AMT) for persistent corneal epithelial defect and sterile ulceration. Case Presentation. A selected case report of a 71-year-old male who underwent primary cryopreserved AMT for the management of long-standing corneal epithelial defects and stroma thinning. The patient developed 2 mm sterile hypopyon within 48 hours after AMT for corneal surface reconstruction. He responded well to the intensified routine postoperative topical treatment of steroid and antibiotic eye drops with the hypopyon resolving completely one week later. Five weeks after surgery, the corneal surface was smooth and epithelialized with no anterior chamber reaction or recurrence of hypopyon. Discussion. Hypopyon may develop as a rare complication of primary cryopreserved AMT for sterile corneal defects. It may be attributed to immunologic or hypersensitivity reaction and should be differentiated from active ocular infection as it resolves spontaneously with the routine postoperative topical treatment of steroid and antibiotic drops.

Corticosteroids in the medical treatment of thyroid ophthalmopathy: when and how? Somatostatin analogues: where we stand today.

Glucocorticoids (GCs) are used for Graves' ophthalmopathy (GO) in two different clinical settings: 1) moderately severe to severe eye disease; and 2) mild eye disease, for which radioiodine therapy is given to treat concomitant hyperthyroidism. Intravenous pulse corticosteroids have a small but statistically significant advantage in terms of response rate compared with oral corticosteroids and cause significantly fewer adverse events. Steroids should be used for as short a period of time as possible. The need for large doses of steroid over a long period of time is a hint that other treatment modalities need to be explored. Combination treatment with oral steroids and ciclosporin, another immunosuppressant, are more efficacious than use of either agent alone. The same applies to combination treatment with oral steroids and orbital radiotherapy. Somatostatin analogues (SM-as) have marginal clinical efficacy and are expensive. More potent analogues, like SOM230, could prove to be the treatment of choice in moderately severe cases of GO. The latter, in contrast to the thus far used analogues, has a rather high affinity for all SM receptors except SM receptor 4.

Orbital fat decompression for Graves' orbitopathy: a literature review.

Thyroid eye disease manifests as orbital inflammation resulting in extraocular muscle enlargement and orbital fat proliferation. This causes exophthalmos, ocular motility impairment and eyelid retraction. Numerous surgical procedures have been introduced for correction of exophthalmos by removal of bony walls. The limited success and high complication rate of the early methods lead to the evolution of an alternative procedure for reduction of retrobulbar volume by removal of intraorbital fat. The indications for this procedure extended from orbital decompression to compressive optic neuropathy with satisfactory results. The moderate complication rate and the fact that orbits with predominant muscle enlargement respond purely to this technique leads to the evolution of a combined procedure with orbital fat removal and bony wall decompression. The scattered published evidence comprising retrospective case series highlights the need for prospective controlled clinical trials in order to improve patient care and clinical practice.

Pediatric aspects in Graves' orbitopathy.

Although pediatric Graves' disease is an uncommon condition, children have about the same (or slightly increased) risk as adults to develop Graves' ophthalmopathy (GO) once they have contracted Graves' hyperthyroidism. GO occurs in the same proportion between sexes but with a milder clinical presentation compared with adults. Lid lag, soft tissue involvement and proptosis are the commonest manifestations, whereas restricted eye muscle motility, severe strabismus and optic neuropathy are practically absent. Genetic, immunologic and environmental factors may be associated with the different appearance of GO in children and adolescents. Interestingly, manifestation of GO begins to resemble the adult findings more closely when adolescence approaches. This could be explained by increasing smoking prevalence with age as long as smoking is a proven to be a risk factor for GO, and the odds increase significantly with increasing severity of GO. Management of hyperthyroidism is essential for the control of complications and seems to offer improvement of eye changes upon restoration of euthyroidism. Antithyroid drugs are the first choice treatment. Lasting remission rates though are achieved in less than 30% of cases. Long periods of therapy are needed and risk for side effects (often serious) increases. In resistant or severe cases early radical treatment with surgery or radioiodine is needed. Both can be equally effective and safe in selected cases. Identification of subjects prone to relapses is critical for optimal management. Regarding treatment of thyroid eye disease in childhood, most physicians who are dealing with such cases prefer a 'wait-and-see' policy. Pharmacological intervention, predominantly with steroids, is considered appropriate in case of deterioration or no improvement of eye changes when the patient has become euthyroid. It has been shown that somatostatin analogs (SM-as) might be of therapeutic value in the treatment of active eye disease in adults. Newer generations of SM-as that target a wider range of somatostatin receptors may show markedly superior results in the treatment of ophthalmopathy. Surgical orbital decompression is hardly ever necessary due to the mild nature of the disease, while retrobulbar irradiation, which has been proved beneficial in adults, has no place in the treatment of juvenile GO, in view of the theoretical risk of tumor induction.

Revisiting Ocular Allergy: Evaluating Symptoms, Benzalkonium Chloride and Efficacy of Topical Ketotifen 0.025.

This interesting study raises a scientific issue for revisiting three important elements on diagnosis, use of preservatives and selection of the appropriate topical treatment. Itchy feeling can be encountered in other ophthalmic conditions misdiagnosed as allergy, benzalkonium chloride is responsible for surface toxicity resulting in reduced efficacy and tolerability of topical allergy medications and it should be avoided on the management of ocular allergy. Unpreserved ketotifen 0,025% has been shown to be the least toxic formulation being the optimum option for efficacy and tolerability on the management of ocular allergy.

Management of canalicular obstructions.

PURPOSE OF REVIEW: The successful treatment of canalicular obstructions continues to represent a therapeutic challenge. Conjuctivodacryocystorhinostomy with a Lester Jones bypass tube is the standard treatment in these situations. Although a high rate of anatomic success can be achieved with this procedure, a relatively high rate of complications and poor patient satisfaction have been reported. Because of this, alternative techniques have emerged. Herein, we review all these techniques described in the literature. RECENT FINDINGS: Increasing interest in minimally invasive surgery and developments in fiberoptic technology have fueled advances in endocanalicular surgery. Canalicular trephination for obstructions at any level of the canalicular system and laser and balloon canaliculoplasty for focal canalicular and common canalicular stenoses may offer a well tolerated, fast and easy alternative, with potentially better patient satisfaction when compared with conjuctivodacryocystorhinostomy. SUMMARY: The alternative techniques to conjuctivodacryocystorhinostomy are less invasive, and respect and utilize any healthy and functional part of the canalicular system. The correct choice of the technique for a given canalicular obstruction, and therefore the long-term success, depends on the site and degree of the obstruction.

Association between vitamin D receptor gene polymorphisms and Graves' disease: a systematic review and meta-analysis.

PURPOSE: The pathogenesis of Graves' disease (GD) and orbitopathy (GO) is not completely elucidated. On the other hand, vitamin D receptor (VDR) gene polymorphisms have been associated with vulnerability to a plethora of chronic autoimmune diseases. The primary aim of this study was to synthesize evidence on the association between VDR gene polymorphisms and GD. Secondary aim was to investigate their association with GO. METHODS: A comprehensive search was conducted in PubMed, CENTRAL and Scopus, up to December 8, 2018. Data were expressed as odds ratio (OR) with 95% confidence intervals (CI). Heterogeneity was quantified with I2 index. RESULTS: Ten studies were included in the qualitative and quantitative analysis. TT subtype of TaqI polymorphism was associated with an increased risk of GD compared with Tt and tt polymorphisms (OR: 1.42; 95% CI, 1.05-1.94, p = 0.025), whereas tt was associated with a lower risk of GD, compared with TT and Tt polymorphisms (OR: 0.79; 95% CI, 0.62-0.99, p = 0.043). No association was found for ApaI, BsmI, and FokI polymorphisms. The bb subtype of BsmI polymorphism was associated with a lower risk in Asian, but with a higher GD risk in Caucasian populations, compared with BB/Bb subtypes. No eligible study was found regarding the association between VDR gene polymorphisms and the risk of GO. CONCLUSIONS: The TT subtype of the TaqI polymorphism was associated with a higher susceptibility for GD compared with Tt and tt. Regarding BsmI, the bb subtype was associated with increased GD risk in Caucasians, whereas it is protective in Asians.

Risk factors for local recurrence of basal cell carcinoma and cutaneous squamous cell carcinoma of the middle third of the face: a 15-year retrospective analysis based on a single centre.

Non-melanoma skin cancer (NMSC) is the commonest malignancy worldwide (>80% located in the head and neck area). The aim of this study was to assess risk factors predisposing to local recurrence of NMSC of the middle third of the face (MTF). This was a single-centre retrospective analysis of patients with NMSC of the MTF treated during 1995-2010. Data on epidemiological and tumour characteristics were collected. Survival analysis was performed and log-rank tests were used to compare differences in survival for each variable. A total of 531 patients with basal cell carcinoma (BCC) of the MTF were identified. Most tumours were nodular type (28.4%), located on the nose (34.3%), and confined to the dermis (75.5%). Negative margins were achieved in 91% of cases. Median follow-up time was 35 months and 15.2% of patients developed local recurrence. Incomplete excision was the only variable predisposing to local recurrence. The cohort also included 114 patients with squamous cell carcinoma (SCC). Most tumours were well differentiated (43.9%), located at the zygomatic area (49.1%), excised with negative margins (93%), and confined to the dermis (67.8%). At a median follow-up time of 42 months, local recurrence occurred in 15.7% of patients. Tumour size, depth of invasion, and prior history of head and neck SCC were risk factors for local recurrence. The variables predictive of recurrence of BCC were incomplete excision and for SCC tumour size, depth of invasion, and a prior history of head and neck SCC.

Meibomian gland inversion: under-recognized entity.

OBJECTIVE: To describe a clinical entity of upper eyelid margin and meibomian gland inversion (MGI) sequential to meibomian gland dysfunction (MGD), in the absence of eyelash ptosis, trichiasis or manifest marginal entropion. We highlight its clinical features, surgical management and outcomes. METHODS: We performed a retrospective analysis of symptomatic MGI cases refractory to conservative management who underwent surgery in our centre over a 4-year period. Anatomical correction, resolution of symptoms and possible complications are reported. RESULTS: A total of 21 eyelids of 13 patients (mean age: 68.5 ± 15.4, range: 32-88 years) were analysed. Symptomatic MGI patients were operated only if they have noted immediate comfort when we corrected the lid margin position with a cotton tip. Those with refractory superior punctate corneal staining (n = 14 eyes), blink-related discomfort (n = 8) and pseudo-blepharospasm (n = 3) reported complete postoperative resolution. Milder symptoms showed partial improvement: gritty feeling (79%), sore eye (80%) and watery eye (86%). However, symptoms of dry eye disease (DED) persisted in 88% of patients. One case recurred in 6 weeks and was offered revision surgery. Median follow-up was 5 (range: 3-12) months. CONCLUSION: Meibomian gland inversion (MGI) is a subtle clinical entity that can be easily overlooked. Symptoms are often attributed to DED or MGD alone. It is likely that MGI represents early upper lid margin anatomical changes secondary to MGD before cicatricial marginal entropion becomes clinically apparent. Recommended treatment is conservative with intensive lid hygiene and topical MGD management. However, refractory symptomatic cases who respond positively to a 'cotton-tip test' (reversal of lid margin malposition with a rolling cotton-tip) may benefit from surgical intervention with favourable anatomical and functional outcome.

Role of corneal nerves in ocular surface homeostasis and disease.

Corneal nerves are key components of the physiological system that controls ocular surface homeostasis. The cornea is primarily innervated by the ophthalmic branch of the trigeminal nerves (cranial nerve V), which distend bilaterally from the pons. The nasociliary branch (afferent) of the ophthalmic nerve is sensory for cornea, eyelid and conjunctiva. These nerve fibres play a role in sensing temperature, chemical and mechanical stimuli, and pain, whereas, branches of the facial nerve (cranial nerve VII) contain motor nerves that control blinking and autonomic (sympathetic and a paucity of parasympathetic) fibres that stimulate tear production and secretion via feedback loops between the ocular surface, lacrimal glands and brain. Disruption of these nerves with interruption of neural feedback loops between the ocular surface and lacrimal glands can lead to corneal diseases such as dry eye disease (DED) and neurotrophic keratopathy (NK). Inversely, hypersensitivity of the nerve fibres and/or dysregulation of pain-controlling nervous centres may lead to neuropathic pain. Recently, medications that specifically target regeneration of corneal nerves have started to become available - and considering the high prevalence of diseases associated with corneal nerve dysfunction, these agents promise to fulfil a hitherto important unmet need. In this review, we explore the physiology of corneal nerves, the pathology of corneal nerve diseases and how these relate to neuropathic pain, NK and DED. We also discuss what novel treatments may be useful against diseases involving corneal nerves.

Cryopreserved amniotic membrane transplantation for the management of symptomatic bullous keratopathy.

BACKGROUND: To report the results of cryopreserved human amniotic membrane transplantation for the management of symptomatic bullous keratopathy. METHODS: Prospective non-comparative interventional case series study. Consecutive cases with symptomatic bullous keratopathy for more than 12 months not amenable to conservative treatment were managed with amniotic membrane transplantation. They were recruited over a 5-year period (September 1999 to November 2004) in one referral centre. Only one eye of each patient (the worse affected eye in bilateral cases) was operated. A 360 degree conjunctival peritomy was followed by removal of the diseased corneal epithelium. Amniotic membrane was transplanted over the cornea as a patch and sutured to the free conjunctival edges. Primary outcome measures were ocular pain and epithelial defects; secondary measures were visual acuity and ocular surface inflammation. RESULTS: Four out of 85 recruited cases did not complete the minimum observation of 12 months and were excluded from the study. The mean follow-up period for the remaining 81 cases was 21 +/- 4.2 months (range 14-34 months). Seventy-one (87.6%) eyes became asymptomatic with healed epithelium, seven required repeated amniotic transplantation and three underwent penetrating keratoplasty. Visual acuity improved in 64 (79%) patients and remained unchanged in 14. No complications were recorded. CONCLUSIONS: Amniotic membrane transplantation is an efficient and safe treatment for symptomatic bullous kerato pathy, when penetrating keratoplasty is not available. It has been shown to alleviate pain, promote corneal epithelialization and reduce conjunctival inflammation whereas in some cases it may also improve visual acuity.

Preservative-Free Prostaglandin Analogs and Prostaglandin/Timolol Fixed Combinations in the Treatment of Glaucoma: Efficacy, Safety and Potential Advantages.

Glaucoma therapy-related ocular surface disease (OSD) is a serious pathology with a broad spectrum of insidious clinical presentations and complex pathogenesis that undermines long-term glaucoma care. Preservatives, especially benzalkonium chloride (BAK), contained in topical intraocular pressure-lowering medications frequently cause or aggravate OSD in glaucoma. Management of these patients is challenging, and to date often empirical due to the scarcity of controlled long-term clinical trials. Most of the available data are extracted from case series and retrospective analysis. Preservative-free prostaglandins and prostaglandin/timolol fixed combinations are novel options developed to remove the harmful impact of preservatives, especially BAK, upon ocular tissues. Based on what is currently known on the value of preservative-free antiglaucoma therapies it is tempting to speculate how these new therapies may affect the future medical management of all glaucoma patients. This article provides a comprehensive and critical review of the current literature on preservative-free prostaglandins and preservative-free prostaglandin/timolol fixed combinations.

Controlled Adverse Environment Chambers in Dry Eye Research.

Dry eye disease (DED) is a common condition with signs and symptoms that vary depending on a wide range of environmental factors to which people are exposed in their daily lives. Factors such as variable temperature, airflow velocity, relative humidity, seasonality, and pollutants can alter the rate of tear film evaporation, improving or exacerbating symptoms of DED. Results from currently available clinical tests do not always correlate well with patient-reported symptoms, and the continually changing environment and variability in DED symptoms present challenges for the design and conduct of clinical trials. Controlled adverse environment chambers allow standardization of temperature, humidity, and airflow and may minimize potential confounding factors in clinical investigations. Their use can promote accurate study of the pathophysiology of DED, discovery of disease biomarkers, and assessment of the effect of various therapeutic approaches on patients' symptoms. Controlled adverse environment chambers have been used to simulate indoor surroundings such as airplane cabins and to test their effects on contact lens wearers. This review summarizes how these chambers may be useful for the development, approval, and differentiation of potential new treatments for DED.