scholarly journals The physicochemical properties of preserved and preservative‐free latanoprost eye drops and their impact on human conjunctival goblet cells

2022 ◽  
Vol 100 (S267) ◽  
Author(s):  
Olivia Müllertz ◽  
Anne Nagstrup ◽  
Zaynab Ahmad Mouhammad ◽  
Josefine Clement Freiberg ◽  
Richard Nagymihaly ◽  
...  
2021 ◽  
pp. 69-75
Author(s):  
Anne Hedengran ◽  
Xenia Begun ◽  
Olivia Müllertz ◽  
Zaynab Mouhammad ◽  
Rupali Vohra ◽  
...  

<b><i>Introduction:</i></b> Most intraocular pressure (IOP)-lowering eye drops are preserved with benzalkonium chloride (BAK). This can increase side effects and decrease adherence. Particularly, damage to the mucin-producing conjunctival goblet cells may be an issue due to instability of the tear film. We aimed to investigate the effect of IOP-lowering eye drops preserved with BAK on cultured human conjunctival goblet cells. <b><i>Methods:</i></b> Eye drops Brimonidine Tartrate Teva (BT) with 0.005% BAK, Dorzolamide Stada (DS) with 0.0075% BAK, Optimol<sup>®</sup> (OP) with 0.01% BAK, and Latanoprost Teva (LT) with 0.02% BAK were included. Human primary cultured goblet cell survival was evaluated using a lactate dehydrogenase assay on human goblet cells after treatment for 30 min and 6 h with the different anti-glaucoma drug formulations. <b><i>Results:</i></b> All eye drops examined, except BT, reduced goblet cell survival. The impact of eye drops on goblet cell viability was correlated with the time of exposure as well as to the concentration of BAK. After 30 min of exposure, cell viability was 93% for BT (0.005% BAK; <i>p</i> = 0.93), 71% for DS (0.0075% BAK; <i>p</i> = 0.067), 70% for OP (0.01% BAK; <i>p</i> = 0.054), and 69% for LT (0.02% BAK; <i>p</i> = 0.022), and exposure for 6 h reduced cell survival to 74% for BT (<i>p</i> = 0.217), 52% for DS (<i>p</i> = 0.011), 34% for OP (<i>p</i> = 0.017), and 31% for LT (<i>p</i> = 0.0007). <b><i>Conclusion:</i></b> LT, OP, and DS reduced human goblet cell survival in a time-dependent manner. BT did not affect goblet cell survival. Cell survival was correlated with the BAK concentration in the eye drops making 0.02% BAK-preserved LT most toxic and 0.005% BAK-preserved BT least toxic. Based on the present study, decreasing BAK in eye drops for chronic use seems important to reduce damage to the goblet cells. However, future studies are needed to further explore this finding.


2013 ◽  
Vol 91 (5) ◽  
pp. e397-e405 ◽  
Author(s):  
Leonardo Mastropasqua ◽  
Luca Agnifili ◽  
Vincenzo Fasanella ◽  
Claudia Curcio ◽  
Cristina Ciabattoni ◽  
...  

2021 ◽  
Vol 6 (1) ◽  
pp. e000892
Author(s):  
Olivia Müllertz ◽  
Anne Hedengran ◽  
Zaynab Ahmad Mouhammad ◽  
Josefine Freiberg ◽  
Richárd Nagymihály ◽  
...  

ObjectiveTo investigate the short-term impact on human conjunctival goblet cell (GC) survival and mucin release of acute exposure to benzalkonium chloride (BAK) preserved and preservative-free (PF) 0.005% (w/v) latanoprost (LT) eye drops, and to compare the eye drops’ physicochemical properties.Methods and analysisPrimary GC cultures were established from human conjunctival donor tissue. The impact of eye drops on GC survival was assessed using a lactate dehydrogenase assay. Mucin release was evaluated through mucin-specific immunostaining. pH value, osmolality, drop mass and surface tension for all LT eye drops were measured.ResultsAfter application with PF-LT for 30 min (min), the GC survival was maintained compared with control (p=0.9941), while all BAK-LT eye drops reduced survival with approximately 30% (p<0.02). Following application with PF-LT for 30 min, mucin was found around the GC nucleus, as seen in the vehicle control, indicating no secretion. In contrast, BAK-LT caused diffuse staining of mucin, similar to the secretagogue histamine, indicating stimulation of secretion. The pH value of the BAK-LT and PF-LT eye drops were 6.0–6.9 and 6.8, respectively. The osmolality was 258–288 mOsm/kg for the BAK-LT eye drops and 276 for PF-LT eye drops. The mean drop mass was 26–31 mg for the BAK-LT eye drops and 30 mg for PF-LT. The surface tension was lower for all BAK-LT eye drops (31.1–32.1 mN/m) compared with PF-LT (42 mN/m).ConclusionPF-LT compared with various branded and generic LT preparations containing BAK are less cytotoxic when applied to cultured GCs.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dai Woo Kim ◽  
Jonghoon Shin ◽  
Chang Kyu Lee ◽  
Myungjin Kim ◽  
Sohyeon Lee ◽  
...  

AbstractGiven that nonadherence is related to subject characteristics and drug tolerance and preserved eye drops tend to be more intolerable than preservative-free ones, we conducted a phase 4, parallel-grouped, investigator-blind, active-control, randomized, multicenter study. A total of 51 patients with intraocular pressure (IOP) ≥ 15 mmHg diagnosed with open-angle glaucoma or ocular hypertension were randomly assigned to the preserved latanoprost group (n = 26) and the preservative-free latanoprost group (n = 25). The efficacy variables were corneal/conjunctival staining grade, Ocular Surface Disease Index (OSDI), adherence at 12 weeks after the first administration; corneal/conjunctival staining grade at 4 weeks; and IOP, tear break-up time (TBUT), and hyperemia score at 4 and 12 weeks. The safety variables included visual acuity and drug tolerance questionnaire results. There was no statistically significant difference in corneal/conjunctival staining grade, OSDI, or TBUT between the groups at 4 and 12 weeks. However, the adherence rate was higher and the hyperemia score was lower in the preservative-free group than in the preserved group. The severity and duration of stinging/burning sensation were lower in the preservative-free group than in the preserved group. Overall, preservative-free latanoprost showed better ocular tolerance assessed by hyperemia scores and stinging/burning symptoms following higher adherence than preserved latanoprost.


Cornea ◽  
2006 ◽  
Vol 25 (5) ◽  
pp. 573-581 ◽  
Author(s):  
José D. Ríos ◽  
Marie Shatos ◽  
Hiroki Urashima ◽  
Hao Tran ◽  
Darlene A. Dartt

1997 ◽  
Vol 235 (11) ◽  
pp. 717-722 ◽  
Author(s):  
Antonio Micali ◽  
Domenico Puzzolo ◽  
Alba M. Arco ◽  
Antonina Pisani ◽  
Giuseppe Santoro ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-11
Author(s):  
Marcella Nebbioso ◽  
Marta Sacchetti ◽  
Guia Bianchi ◽  
Anna Maria Zicari ◽  
Marzia Duse ◽  
...  

Background. Vernal keratoconjunctivitis (VKC) is a rare ocular surface inflammatory disease that affects mainly boys in the first decade of life. Clinical observations show that it generally regresses spontaneously with the onset of puberty, but therapeutic measures must be taken before then to control the course of the disease. Purpose.To evaluate the role of the lacrimal mucous component in VKC patients and compare tear ferning test (TFT) modifications, MUC5AC levels in tears, and density of conjunctival goblet cells to clinical characteristics before and after treatment with cyclosporine A (CY) in eye drops. Methods. Forty-seven patients affected by VKC and 30 healthy subjects aged between 3 and 16 years of life were enrolled. All individuals were submitted to complete eye examination and skin prick test (SPT) for the most common allergens. Then, they were subjected to collection of the tears and to impression cytology to evaluate TFT, MUC5AC levels, and conjunctival goblet cell density, before and after treatment with CY in eye drops. Results. Comparing the VKC group vs. the control group at baseline, a significant alteration in the degree of the ferns was found, indicating a pathological condition of the lacrimal mucous layer. In addition, an increased number of goblet cells were observed in the patients. The concentration of lacrimal secretory mucins (MUC5AC) did not show significant differences between the 2 groups. Patients treated with CY have reported improvements of some signs and symptoms of disease activity, including TFT, and a tendency of conjunctival goblet cell density to normalise. Conclusions. The results obtained demonstrated for the first time a significant alteration of the lacrimal mucin component evaluated in the VKC group, and an improvement of the latter after CY therapy.


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