Model development of aqueous deficient dry eye secondary to periglandular cicatrizing conjunctivitis.

PURPOSE: The current study used various techniques to develop a rabbit animal model of lacrimal gland damage caused by scarring conjunctivitis in the periglandular area. METHODS: Left eyes of New Zealand white rabbits were injected with 0.1 ml of 1M NaOH subconjunctivally around superior and inferior lacrimal gland orifices (Group 1, n = 4), touched with 1M NaOH for 100 s to the superior and inferior fornices with conjunctival denuding (Group 2; n = 4), and electrocauterization to the ductal opening area (Group 3; n = 4). The ocular surface staining, Schirmer I, lacrimal gland, and conjunctival changes were observed at baseline,1, 4, 8, and 12 weeks. The degree of glandular inflammation, conjunctival fibrosis (Masson Trichrome), and goblet cell density (PAS) were also assessed. RESULTS: At 12 weeks, the lacrimal glands of group 1 rabbits with periglandular injection showed severe inflammation with mean four foci/10HPF and a significant mean reduction in the Schirmer values by 7.6 mm (P = 0.007). Lacrimal glands had diffuse acinar atrophy, loss of myoepithelial cells, and ductular dilatation. The overlying conjunctiva showed fibrosis, goblet cell loss, and corneal vascularization in the inferotemporal quadrant. No lacrimal gland or ocular surface changes were observed in groups 2 and 3 at 12 weeks, except for localized subconjunctival fibrosis. CONCLUSION: Periglandular injection of 0.1 ml of 1M NaOH induced extensive lacrimal gland damage with reduced secretion and scarring in the subconjunctival plane compared to direct cauterization or direct NaOH contact to the ductal orifices of the rabbit lacrimal gland.

Lacrimal gland activity in lacrimal drainage obstruction: exploring the potential cross-talk between the tear secretion and outflow.

PURPOSE: To investigate the effects of lacrimal drainage obstructions on the lacrimal gland activity and if there exists a potential link between the two. METHODS: Direct assessment of the lacrimal gland activity from the palpebral lobe was performed in consecutive patients diagnosed with unilateral primary acquired nasolacrimal duct obstruction (PANDO), along with Ocular Surface Disease Index (OSDI), non-invasive tear break up time (NIBUT; Oculus K5M), tear meniscus height and Schirmer I. The primary outcome measure was the difference in the tear flow rate between the eye with PANDO and the contralateral uninvolved eye. RESULTS: Thirty patients (median age, 45.5 years; 25 females) with unilateral PANDO had epiphora for a mean duration of 20 months. The mean OSDI score was 6.3. NIBUT (mean 11.56 vs 11.58 s; p=0.49) and Schirmer I values (mean 18.83 vs 19.4 mm; p=0.313) were not significantly different between PANDO and non-PANDO eyes. The morphology of the palpebral lobe (size 29.3 vs 28.6 mm2, p=0.41) and the number of lacrimal ductular openings (median 2 vs 2.5) were similar between the two eyes. The mean tear flow from the lacrimal glands of the PANDO side was significantly reduced compared with the contralateral uninvolved side (0.8 vs 0.99 µL/min; p=0.014)). CONCLUSION: Tear flow rate from palpebral lobes of patients with unilateral lacrimal outflow obstruction shows a significant reduction compared with the contralateral side. The potential ways of communications between the tear drainage and the tear production mechanisms need to be explored further.

Resolving fetal hydrops - A rare entity.

Non-immune hydrops fetalis (NIHF) is abnormal accumulation of serous fluid in ≥2 interstitial spaces with no evidence of maternal red cell alloimmunization. Leaving a few treatable conditions, it is generally considered as a sign of poor fetal outcome. Bi-allelic variants in THSD1 have been found to be to be associated with phenotypes ranging from lethal NIHF to persistent edema. Here, we report a family with non-immune hydrops in two successive pregnancies. Whole exome sequencing in second pregnancy identified a homozygous truncating variant in THSD1 (NM_018676:c.892G>T:p.Glu298Ter). Postnatal follow up showed gradual resolution of the accumulated fluid and normal development. This report further strengthens the association of variants in THSD1 with NIHF.

Morphologic variants of Meibomian glands: age-wise distribution and differences between upper and lower eyelids.

Purpose: To evaluate the distribution of various Meibomian gland morphologies across different age groups in healthy individuals. Methods: The infrared meibographic morphologies of the Meibomian glands from the upper and lower eyelids of 236 healthy individuals (472 eyes; mean age 38.4 ± 17.5 years; 80 female participants: 156 male participants) were evaluated for their prevalence and differences across six decades of life, from 10 to 80 years. A linear mixed-effects modeling test was performed for statistical analysis. Results: Of 14,452 glands, 8,830 (61%) glands were located in the upper eyelid. No significant differences in frequency were noted between different age groups for distorted, tortuous, hooked, overlapping, abnormal gap, fluffy areas, dropout (except for 51-60 vs. 10-20 years, P = 0.023), and thick and thin morphologies. Short glands were significantly more common in individuals aged over 30 years (P = 0.015), whereas moderately short and severely short glands were more common in the upper eyelids of individuals older than 50 years compared to those aged 10-20 years (P = 0.035). The frequency of distorted, hooked, tortuous, overlapping, and tadpole-shaped Meibomian glands was significantly higher in the upper eyelids than in the lower eyelids for all age groups. Dropout glands were more common in the lower eyelids of individuals younger than 50 years, but no difference was observed in the upper and lower eyelids of individuals over 50 years. Dropout (P = 0.006) and severely short glands (0.026) of the lower eyelid were associated with low non-invasive tear break-up time (NIBUT) values. Conclusion: Various morphologic characteristics of the Meibomian glands that are considered abnormal can be present in healthy individuals, and only moderate to severely short glands display an increase in abnormal morphologic characteristics of the Meibomian glands with age.

Tear film changes in symptomatic versus asymptomatic video display terminal users following computer challenge test.

PURPOSE: To assess the real-time changes in the tear film and ocular surface of symptomatic video display terminal (VDT) versus asymptomatic users. METHODS: A total of 35 symptomatic (29 ± 5.6 years; Group 1, mild dry eye disease) and 35 asymptomatic (24.1 ± 4.6 years; Group 2) VDT users with a mean OSDI of 28 ± 11 and 0.86 ± 2.1, respectively, had tear film examination (Oculus Keratograph 5 M and Tearlab Osmolarity System) at baseline and after 1 h of watching a movie on the laptop inside a controlled environment chamber along with blink rate calculation. RESULTS: The mean VDT use was 11.4 ± 3.2 h/day in Group 1 and 2.3 ± 2.3 h/day in Group 2. In Group 1, the mean pre- and post-VDT task values for NIBUT and bulbar congestion were 10.7 ± 3.7s and 6.7 ± 3.1s (P = 0.007), and 0.8 ± 0.4 and 1.1 ± 0.5 (P = 0.01), respectively. There were no significant changes in tear meniscus height (P = 0.77), Schirmer I (P =0.14), corneal staining score (P = 1.0), and tear osmolarity (P > 0.05). Group 2 showed insignificant change in all parameters. Only 16.2% individuals in Group 1 met modified TFOS-DEWS II diagnostic criteria at baseline that increased to 67.6% following VDT task. The blink rate reduced significantly during the last 15 min (6.8 ± 3.4 vs. 9.3 ± 4.5; P = 0.006) compared to the first 15 min of the task in Group 1, whereas no significant change occurred in Group 2. CONCLUSION: Tear film instability and increased bulbar congestion are observed in symptomatic VDT users after computer work despite baseline stable tear film. The changes are significantly altered in symptomatic VDT users compared to asymptomatic users.

Repeatability of Non-invasive Tear Film Evaluation in Healthy Rabbit Eyes.

PURPOSE: The current study investigated the normative data values and repeatability of non-invasive tear film tests using Oculus Keratograph 5M in rabbit eyes. METHODS: Triplicate analysis of tear film parameters [tear meniscus height (TMH), non-invasive tear break up time (NIBUT), bulbar congestion, meibography] of 38 healthy adults New Zealand white rabbits (mean age, 13 ± 4.7 months) was performed using Oculus keratograph 5M (K5M). Bland-Altman analysis was used for testing repeatability. RESULTS: Thirty-eight rabbits (N = 76 eyes) weighing 2.5 ± 0.4 kg were studied. The mean NIBUT values of the right and left eye were 14.3 ± 5.8 and 12.3 ± 5.8 s, respectively. The mean central TMH values were 0.43 ± 0.23 and 0.33 ± 0.14 mm in the right and left eye, respectively. Meibography showed closely placed, wide meibomian glands running vertically with no distorted or gland loss areas. There were no differences between the eyes for the above parameters. Bland-Altman plot showed good repeatability for both NIBUT and TMH values. CONCLUSION: The non-invasive tear film parameters show good repeatability using keratograph 5M and can be used as an objective parameter for rabbit ocular surface experiments.

Lacrimal and meibomian gland evaluation in dry eye disease: A mini-review.

Lacrimal and meibomian glands contribute to the aqueous and lipid components of tear film, respectively. Their evaluation remains central to diagnosing and managing dry eye disease (DED). The review discusses the differences and reliability of various diagnostic tests and commercially available devices used for DED diagnosis. Slit-lamp-based techniques are direct palpebral lobe and tear flow assessment, Schirmer test, meibum quality and expressibility, and evaluation of tear meniscus height. Non-invasive tear meniscus height (TMH), tear break-up time (TBUT), lipid layer thickness (LLT), and meibography are machine-based diagnostic tests. The structure-function correlation of the tear-producing glands gives more comprehensive details than either information alone. Many devices are available in the market, which make DED diagnosis an easy feat, but the tests should be interpreted keeping in mind the intra-observer and inter-observer repeatability. Also, the tear film displays a huge variability as per the environmental conditions and impact of blinking. Hence, the examiner should be well versed with the techniques and repeat the test two to three times to obtain an average reading, which is more reliable. The recommended sequence of tests for diagnosing DED is a dry eye questionnaire, TMH, LLT, NIBUT (FBUT if non-invasive test is unavailable but should be performed after osmolarity), tear osmolarity, meibography, and ocular surface staining. Invasive tests such as Schirmer should be performed after the non-invasive tear film diagnostic testing.

Repeatability, reproducibility and agreement between three different diagnostic imaging platforms for tear film evaluation of normal and dry eye disease.

PURPOSE: To assess the repeatability and reliability of different commercially available diagnostic platforms in the objective assessment of tear film parameters and if there exists any agreement between them. METHODS: Thirty healthy individuals (N = 60 eyes) and fifteen DED patients (N = 30 eyes) had their tear film parameters (Lipid layer thickness (LLT), Tear meniscus height (TMH), Non-invasive tear break up time (NIBUT)) assessed using three instruments - LipiView® II, IDRA ocular surface analyser (IDRA-OSA) and Oculus keratograph 5 M (K5M). Bland-Altman analysis and linear mixed effects modelling & Generalized Linear Hypothesis Test were used for analysis and coefficient of variation (CoV). RESULTS: There is poor repeatability but good reproducibility of LLT values measured with Lipiview, or IDRA. NIBUT using K5M & IDRA-OSA shows good repeatability and reproducibility in control group but poor repeatability in DED patients. TMH values obtained with K5M or IDRA-OSA had poor repeatability with high CoV. Between two observers, good reproducibility is observed for TMH and NIBUT values using both K5M & IDRA-OSA but not for LLT values. Between instruments, all the measurements (LLT, NIBUT and TMH) were significantly different on Bland Altman analysis. CONCLUSION: No two dry eye diagnostic platforms can be used interchangeably and non-invasive tear film values should be interpreted keeping in mind the individual machine's variability. The high coefficient of variation in DED patients compared to normal reflects inherent variability in tear film irrespective of the device used.

Non-invasive Tear Film Assessment in Normal Population: Effect of Age, Sex, and Interparametric Relationship.

Purpose: To investigate age- and sex-related differences in tear film parameters of normal Indian population and study interparametric relationships. Methods: Healthy subjects with no ocular disease (median ocular surface disease index = 0) were subjected to an automated evaluation of tear meniscus height (TMH), non-invasive tear breakup time (NIBUT) using Keratograph 5M (OCULUS GmbH, Wetzlar, Germany), and tear osmolarity using the TearLab Osmolarity System (TearLab Corporation, California, USA). A mixed-effects model with random intercepts at the patient level was used to evaluate the relationships between explanatory (age, gender, and tear osmolarity) and outcome variables (TMH and NIBUT). Results: A total of 237 subjects (474 eyes; 150 males) were enrolled with a mean age of 40 ± 17 years (range, 10-78 years). The mean values (± standard deviation) of TMH, NIBUT, and tear osmolarity were 0.34 ± 0.07 mm, 10.95 ± 2.02 s and 289.0 ± 5.8 mOsm/L, respectively. Age had a significant positive relationship with TMH (p < 0.0001; 0.002 mm/year; r = 0.12), but there was no effect on NIBUT (p = 0.26) and tear osmolarity (p = 0.27). There were no sex-based differences in tear film parameters. Interparametric relationship revealed no significant association between TMH and NIBUT (p = 0.12) or tear osmolarity and TMH (p = 0.83) or tear osmolarity and NIBUT values (p = 0.48). Conclusions: In a normal Indian population, TMH is weakly affected by age and is independent of sex, NIBUT, and tear osmolarity. Tear breakup time and osmolarity show no significant age- and sex-related variation.