Application frequency - key indicator for the efficiency of severe dry eye disease treatment - evidence for the importance of molecular weight of hyaluronan in lubricating agents.

PURPOSE: Lubricant eye drops are the main therapeutic resource for dry eye disease (DED), with each drop representing the equivalent of ocular surface disease treatment. Thus, any reduction in the frequency of eye drop application reflects a degree of therapeutic success. Considering also the socioeconomic burden of DED, we investigated eye drop application frequency (DF) as a parameter to potentially track the success of therapy in severe DED. Hyaluronan (HA)-containing eye drops have become the first choice for tear substitution in many countries, and recent data indicate that the average molecular weight (Mw) of HA determines the therapeutic efficacy of such eye drops. This post-hoc subgroup analysis of a previously published multicentre prospective randomized open-label study, HYLAN M, is set out to compare the effects of very high Mw HA (hylan A) eye drops to comparator eye drops, containing lower Mw HA (control). METHODS: Patients with severe DED (n = 47), recruited as part of the larger HYLAN M prospective, multicentre, open-label study, were randomized into two groups: hylan A and control group. In the hylan A group, 24 patients replaced their HA-containing eye drops with eye drops containing 0.15% hylan A, whereas the 23 control patients continued to use comparator HA eye drops. The DF was recorded daily by all participants over 8 weeks, and other subjective and objective parameters of DED were assessed at the time of inclusion (baseline), as well as at week 4 and 8. RESULTS: There was a significant decrease in DF in the hylan A users between the baseline and week 4 (p = 0.004), remaining stable until week 8. Indeed, in contrast to the baseline, the hylan A group had a significantly lower DF than the control group at weeks 4 (p = 0.018) and 8 (p = 0.008). Likewise, the ocular surface disease index (OSDI) improved significantly between the time of inclusion and week 4 (p < 0.001) in hylan A users, remaining stable until week 8. The OSDI was similar in both groups at the baseline but it was significantly lower in the hylan A group than in the control group at week 4 (p = 0.002), remaining lower at week 8. Such a decrease in the DF and OSDI was not witnessed in the control group at any time point. The objective parameters assessed did not differ significantly within or between the two groups. CONCLUSION: When treating severe DED, the DF can be significantly reduced by using very high Mw HA (3 MDa) lubricant eye drops, which better alleviate DED symptoms and decrease the OSDI scores. These drops not only provide an attractive and comfortable alternative for patients with severe DED but also offer the possibility of reducing the disease's socioeconomic burden, both for affected individuals and society as a whole.

Neuropathic Corneal Pain as Debilitating Manifestation of LONG-COVID.

This report illustrates the case of a female patient suffering from severe ocular discomfort, tinnitus and ageusia, 7 months after a SARS-CoV-2 infection. The medical history implicated a diagnosis of LONG-COVID with ocular pain as the most debilitating symptom. In-vivo confocal microscopy revealed corneal microneuromas with hyperreflectivity and irregular enlargement of nerve endings in both eyes, which led to the diagnosis of neuropathic corneal pain. The aim of this report is to increase awareness that COVID-19 induced neuropathic pain can also occur in the cornea representing the human body's most richly innervated tissue.

Demodex Mite Infestation and its Associations with Tear Film and Ocular Surface Parameters in Patients with Ocular Discomfort.

PURPOSE: The presence of Demodex species can be associated with blepharitis. Their pathogenic potential in meibomian gland dysfunction is discussed herein. The purpose of this study was to determine the prevalence of Demodex mites in eyelashes of Austrian patients with ocular discomfort and to evaluate associated changes of the lid margins and meibomian glands. DESIGN: This is a case-control study. METHODS: Two hundred twenty-nine consecutive patients with ocular discomfort from an Austrian dry eye clinic were investigated for the presence of Demodex mites on sampled eyelashes. Associations of a mite infestation with individual dry eye and lid parameters were assessed. Lid margins were evaluated for scales, vascularization, Marx line, expressibility and quality of meibum, and drop-out of meibomian glands. RESULTS: Demodex mites were identified in 40.2% of patients suffering from ocular discomfort (mean mite count 3.3 ± 2.9 per patient). Infestation with mites was associated with the presence of significantly more cylindrical scales (sleeves), a higher Marx line score, and a lower quality of meibum compared with mite-free patients. There were no significant associations with the expressibility and the drop-out of meibomian glands. CONCLUSION: The prevalence of Demodex mites in patients with ocular discomfort is high. The mean mite count per patient in this Austrian dry eye unit population is lower compared with previously published data from Asian regions. The infestation of the eyelids with Demodex species is associated with changes of the anterior and posterior lid margin, suggesting a pathogenic role in blepharitis and meibomian gland dysfunction.

The prevalence of meibomian gland dysfunction, tear film and ocular surface parameters in an Austrian dry eye clinic population.

PURPOSE: The purpose of this study was to assess the prevalence of meibomian gland dysfunction (MGD) and its association with tear film and ocular surface parameters in an Austrian clinical population of dry eye patients. METHODS: The records of 1372 consecutive patients from a dry eye unit were analysed retrospectively. Symptoms and objective tear film and ocular surface parameters were evaluated. Patients were classified into pure MGD, pure aqueous tear deficiency (ATD), MGD combined with ATD, pure anterior blepharitis (AB), Sjogren's syndrome (SS) without MGD and SS together with MGD. RESULTS: Nine-hundred and sixty-five patients, that is 70.3% of the investigated population, mean age 55.4 ± 16.6 years, had signs of MGD. Of these, 684 (70.9%) were female. The intensity of symptoms did not differ between subgroups. Four hundred and ninety (50.8%) MGD patients had Schirmer test values ≤10 mm/5 min. The fluorescein break-up time and Schirmer test values were significantly higher in the pure AB and MGD group. The pure MGD group showed a significantly lower fluorescein staining of the cornea compared to the other groups, except for pure AB. Lissamine green staining of the ocular surface was present in all groups, but was at least pronounced in the pure MGD and AB group. CONCLUSION: Meibomian gland dysfunction is a major cause of ocular discomfort and could often be found in combination with a reduced aqueous tear secretion. Although the intensity of subjective complaints was similar to all other subgroups, pure MGD exhibited the lowest severity of signs of ocular surface damage and also affected younger people.

The Impact of Visual Guided Order Picking on Ocular Comfort, Ocular Surface and Tear Function.

PURPOSE: We investigated the effects of a visual picking system on ocular comfort, the ocular surface and tear function compared to those of a voice guided picking solution. DESIGN: Prospective, observational, cohort study. SETTING: Institutional. STUDY POPULATION: A total of 25 young asymptomatic volunteers performed commissioning over 10 hours on two consecutive days. MAIN OUTCOME MEASURES: The operators were guided in the picking process by two different picking solutions, either visually or by voice while their subjective symptoms and ocular surface and tear function parameters were recorded. RESULTS: The visual analogue scale (VAS) values, according to subjective dry eye symptoms, in the visual condition were significantly higher at the end of the commissioning than the baseline measurements. In the voice condition, the VAS values remained stable during the commissioning. The tear break-up time (BUT) values declined significantly in the visual condition (pre-task: 16.6 sec and post-task: 9.6 sec) in the right eyes, that were exposed to the displays, the left eyes in the visual condition showed only a minor decline, whereas the BUT values in the voice condition remained constant (right eyes) or even increased (left eyes) over the time. No significant differences in the tear meniscus height values before and after the commissioning were observed in either condition. CONCLUSION: In our study, the use of visually guided picking solutions was correlated with post-task subjective symptoms and tear film instability.

Prevalence of canaliculitis after smartplug insertion during long-term follow-up.

PURPOSE: To evaluate the long-term prevalence of canaliculitis associated with the use of SmartPlugs. METHODS: This retrospective study included 42 eyes of 25 dry eye patients at our institution who received a SmartPlug insertion between 2004 and 2008. Irrigation of the lacrimal system was performed in all patients prior to SmartPlug insertion to ensure the patency of the system. The median follow-up time was 7.9 (5.6-10.5) years after plug insertion. RESULTS: Six patients (seven eyes) of 25 patients (42 eyes) developed canaliculitis. The prevalence of canaliculitis per patient was 24%, and the prevalence of canaliculitis per SmartPlug was 16.6%. The median time from SmartPlug insertion to the onset of canaliculitis was 4.7 (1.4-6.0) years. The median age of the affected patients was 61.5 (36-74) years. Five of these patients were women and one was man. The pathogens were identified as Actinomyces in four eyes and as Staphylococcus aureus in three eyes. In five patients (six eyes), the canaliculitis was resolved by the application of topical antibiotics and repeated lacrimal irrigations with antibiotics and povidone-iodine. In one patient, a canaliculotomy was necessary to cure the condition. CONCLUSIONS: The late onset of complications after SmartPlug insertion requires long-term observation to identify the majority of complications associated with SmartPlugs. In our patients with a follow-up of up to 10.5 years, the use of SmartPlugs was associated with the highest prevalence of canaliculitis published thus far.

Evaluation of ocular surface and tear film function following modified Hughes tarsoconjunctival flap procedure.

PURPOSE: To evaluate ocular surface characteristics and tear film function following modified Hughes flap for eyelid reconstruction. METHODS: This is an institutional study including 18 patients (6 male, 12 female) who underwent a tarsoconjunctival flap for reconstructing the lower eyelid's posterior lamella in one eye between 2005 and 2010. The median age of the patients was 72 (49-93) years at the time of surgery and 77 (51-97) years at the time of evaluation. The median follow-up time was 34 (9-69) months. All patients had large malignant or semi-malignant lid tumours. Data for subjective symptoms (OSDI questionnaire), lid margin morphology, tear break-up time (BUT), vital staining, Schirmer test, impression cytology, tear film osmolarity, lipid layer interference patterns, meibography and the size of the tumour and flap were recorded and compared with the contralateral side. RESULTS: Statistical analysis of the data revealed a significant difference between the surgically treated lid and the untreated side in meibomian gland loss, more lid margin abnormalities in the upper and lower eyelid (p<0.001) and increased fluorescein staining of the cornea (p=0.031). For the operated side, the median OSDI score was higher (17.2 versus 14.7), and the median BUT value was shorter (4.2 versus 5.6 seconds) compared with the median values of the contralateral side. CONCLUSION: Despite the favourable cosmetic and functional results of the Hughes tarsoconjunctival flap, our results indicate that this procedure does affect the ocular surface health in the treated eyes.

Collared silicone punctal plugs compared to intracanalicular plugs for the treatment of dry eye.

AIM: To compare collared silicone punctal plugs to intracanalicular SmartPlugs for the treatment of moderate to severe dry eye. MATERIALS AND METHODS: In this prospective, randomized, single blind, clinical study, 30 patients (60 eyes) who had been diagnosed with moderate to severe dry eye syndrome were enrolled. Study group I (n = 30 eyes) received collared silicone punctal plugs and group II (n = 30 eyes) received intracanalicular SmartPlugs. Data for the Schirmer I test, tear break-up time, vital staining, subjective symptoms and frequency of artificial tear application were recorded at baseline and 3 months after punctal occlusion. RESULTS: There was no statistical significant difference for these values between group I and II. CONCLUSIONS: Although published data show free flow with irrigation and probing after SmartPlug insertion, the clinical effect in the treatment of dry eye appears to be the equally well to collared silicone punctal plugs. It seems likely that difference of design and localization between the treatment groups were of minor importance concerning impeding of natural and supplemental moisture.

Influence of single-fraction Gamma-Knife radiosurgery on ocular surface and tear function in choroidal melanoma patients.

AIM: To evaluate ocular surface and tear function in patients with choroidal melanoma treated with single-fraction radiosurgery. METHODS: 36 patients (median age 62 years; range 26-84 years) were enrolled between 2001 and 2006 at a single institution. They were treated with the Leksell Gamma Knife in one fraction with a median dose of 30 Gy (range 25-35 Gy). In both eyes of all patients treated subjective symptom score (visual analogue scale) was evaluated, central corneal sensitivity testing, Schirmer test without local anaesthesia, and corneal and conjunctival staining were performed before therapy and 3, 6, 12, 24 and 36 months thereafter. The respective untreated fellow eye served as control. RESULTS: Three months after radiosurgery, the subjective dry eye symptom score and lissamine green staining score of the ocular surface were significantly higher in the treated eyes compared with the fellow eyes (p<0.001, p=0.028, respectively). After 12 months, a significant difference between the treated and the fellow eyes in corneal sensitivity (p=0.041) and corneal fluorescein staining (p=0.002) was found when compared with pretreatment values. After 24 months Schirmer test values without local anaesthesia were significantly reduced in the treated eyes vis-à-vis untreated fellow eyes and pretreatment values (p=0.004). The dose applied to the lacrimal gland was significantly correlated to ocular surface staining scores (p=0.001) and Schirmer test values (p=0.026) at 24 months after irradiation. CONCLUSIONS: Stereotactic single-fraction Gamma-Knife radiotherapy of choroidal melanoma with a median dose of 30 Gy significantly affected ocular surface and tear function and increased dry eye symptoms and signs.

Introducing a new parameter for the assessment of the tear film lipid layer.

PURPOSE: The differential diagnosis of dry eye syndrome is still a challenging task. The purpose of this study was to understand the relationship between a novel, objective clinical parameter, the "corrected lipid layer stabilization time," and commonly performed clinical tests for dry eye patients. METHODS: Data were obtained from a prospective clinical study with 59 patients of different subjective severity, as determined with the Ocular Surface Disease Index (OSDI). The dynamics of the tear film lipid layer were made visible through a white light source and were stored digitally. Because the distance between the upper and lower eyelid affects the lipid layer dynamics and varies significantly between subjects, the distance of the eyelids was determined and used to correct the lipid layer stabilization time. The resulting parameter was compared with common clinical procedures. RESULTS: The corrected lipid layer stabilization time has a highly significant correlation with tear film breakup time (Spearman r = -0.485, P < 0.01), Schirmer test without anesthesia (r = -0.431, P < 0.01) and with the Ocular Surface Disease Index (r = 0.498, P < 0.01). It also correlates with the lissamine green staining score (r = 0.379, P < 0.05), but shows no correlation with the osmolarity of the tear film. Without the correction for the eyelid opening, the correlations decrease considerably. CONCLUSIONS: These data suggest that the diagnostic value of the lipid layer stabilization time for the assessment of the severity of dry eye syndrome increases considerably when it is corrected by the distance of the eyelids.

Long-term follow-up of punctal and proximal canalicular stenoses after silicone punctal plug treatment in dry eye patients.

PURPOSE: To determine the clinical value and relevance of punctal and proximal canalicular stenoses after punctal plug therapy in moderate to severe dry eye syndrome. DESIGN: Retrospective, observational case series. METHODS: Seventeen eyes were determined to have punctum or proximal canalicular stenoses after spontaneous loss of a collared silicone punctal plug. After initial diagnosis all patients had 12 months or more of follow-up (mean, 39; range, 12 to 87 months). The clinical data collected included gender and age of patients, localization of the stenosis, plug size, duration of punctal occlusion, subjective symptoms, objective ocular surface disease parameters, and occurrence of complications. RESULTS: A statistically significant correlation between localization of the stenosis and plug size, and localization of the stenosis and duration of punctal occlusion could not be found. At follow-up, subjective symptoms (P < .01) and frequency of artificial tear application (P < .001) were significantly reduced compared to data before plug insertion. Schirmer I test results (P < .001), corneal fluorescein staining (P < .01), and rose bengal staining (P < .001) improved significantly, whereas tear break-up time (P < .2) and impression cytology scores of the conjunctival surface (P = .2) remained almost unchanged. Complications could not be found. CONCLUSION: Within the observation period of up to seven years, all stenoses remained asymptomatic. Additionally, subjective symptoms and most dry eye parameters in our study population improved.

Long-term retention rates and complications of silicone punctal plugs in dry eye.

PURPOSE: To evaluate long-term retention rates and complications of silicone punctal plugs among dry eye patients. DESIGN: Prospective, observational cohort study. METHODS: Ninety-five silicone punctal plugs (FCI plugs; FCI Ophthalmics, Issy-les-Moulineaux Cedex, France) were placed in 93 eyes of 47 dry eye patients. Within the observation period of up to eight years, this survey included recording of the retention rate, spontaneous loss, removal, canalicular permeability after loss or removal, as well as other complications such as infection, intrusion, and granuloma. RESULTS: The retention rate of the plugs was 84.2% after three months, 69.5% after one year, and 55.8% after a median of two years (range, 17 to 93 months). No infection was observed, but granulomatous formation occurred in three eyes (one with extrusion, two with intrusion). Three plugs had to be removed for local discomfort or epiphora, and one piece of a broken plug intruded. Canalicular stenosis after spontaneous loss occurred in 14.3% after three months, in 26.9% after one year, and in 34.2% after a median of two years. CONCLUSIONS: The retention rate after a median of two years of FCI punctal plugs was satisfactory with few complications. The major observation concerned canalicular stenosis after spontaneous loss.

Five-year results of prognostic value of tyrosinase in peripheral blood of uveal melanoma patients.

Tyrosinase-based reverse transcriptase-polymerase chain reaction (RT-PCR) is a method for the detection of circulating melanoma cells in peripheral blood. To our knowledge, no long-term studies on the prognostic impact of tyrosinase PCR in uveal melanoma have yet been reported. In this prospective, non-randomized, observational cohort study, we included 41 patients with uveal malignant melanoma. RT-PCR for tyrosinase was performed in each patient before and after treatment. A clinical follow-up was performed for each patient for at least 5 years, including chest X-ray, serum liver enzyme determination, ultrasound of the liver and bone scintigraphy. The PCR results, age of the patients, tumour size, tumour location, tumour therapy, internal reflectivity, histology, development of distant metastasis and survival rate during follow-up were analysed. At the time of diagnosis, tyrosinase messenger RNA (mRNA) in peripheral blood, suggesting the presence of circulating melanoma cells, was detected in 16 of the 41 patients. Sixty-nine percent of the PCR samples with a positive result prior to therapy revealed a negative result after therapy. The internal reflectivity of the tumour (P=0.021) and the 5-year survival (P=0.023) showed a statistically significant association with positive PCR. It can be concluded that tyrosinase RT-PCR is a sensitive method for the detection of melanoma cells in peripheral blood. This study indicates that the presence of tumour cells in peripheral blood correlates with 5-year survival. Our results suggest a prognostic value of this method. Nevertheless, prospective analysis of a larger cohort is needed to determine the ultimate value of RT-PCR for tyrosinase in blood testing.