Wednesday, March 7, 2018

Abstract: Glaucoma drop study and another nail in the BAK coffin... right?

I enjoyed reading this study titled "Exploring topical anti-glaucoma medication effects on the ocular surface in the context of the current understanding of dry eye" (scroll down for the abstract)

On the face of it, it is all about glaucoma drops and dry eye. But don't be fooled by the absence of the word "preservative" in the text of the abstract. I checked with the authors to verify a few details because the complete text had not yet been released. As suspected, the paper is really mostly about the known and despised toxic effects of the preservative benzalkonium chloride (BAK), also known as dry eye inducing poison for your eyes.

There is a plethora of literature on the toxic effects of BAK to the cornea. Much of the attention has been given to BAK in the context of glaucoma medication. This is presumably because glaucoma patients (1) have to take drops every day for years, which means long term exposure to the risks, and (2) are older, which means they are already at higher risk, even without additional risk factors common in their age group, such as cataract surgery and the many health conditions requiring medications that are known to be drying to the eyes. Why would we put people to this kind of long term completely avoidable risk? On the other hand, there's probably a much simpler reason for the proportionally high attention to glaucoma drops: (3) glaucoma patients are relatively easy to study as there's so many of them, and they have to take the drops. Bit of a captive audience.

In relatively recent years, preservative free glaucoma medications began seeping onto the market and - much too slowly - began displacing the preserved ones. I remember the first PF glaucoma drop - Travatan Z - and how long it took before I ever heard from dry eye patients whose doctors prescribed it without specifically being asked to by the patient. (You'd think the glaucoma doctors and the cornea doctors might at least occasionally chat over a water cooler?) Thankfully, things are much better now than they were. - That is, specifically in the world of glaucoma medications, and specifically in the US. (Dr Craig mentioned that no preservative free publicly funded options are available yet in New Zealand.)

One of the areas I continue to be very, very concerned about when it comes to dry eye and corneal damage from BAK overexposure is in over-the-counter eyedrops in the US. Drugstore shelves are crammed with all kinds of BAK preserved drops, ranging from lubricants to antihistamines to vasoconstrictors - plus, my most hated crowd: the combo multi-purpose drops. A little bit of lubricant, a vasoconstrictor, an antihistamine, pick a random collection of benefits, stir them up and put a pretty label on them. The majority of such drops are preserved with BAK and as such they pose serious risks to people who buy them and use them regularly.

To me this is a painful failure on the part of the FDA as the warning language in the packaging is completely inadequate. Drops that promise relief of irritation and redness should not contain substances that are known to cause harm if you continue using them. Many of the people these drops are marketed to rarely visit an eye doctor because the level of eye irritation is not severe. There is no one to tell them they are in harm's way.

Anyway, circling back to glaucoma: If you are using glaucoma drops, and you do not know whether they are or aren't preserved, please find out, and talk to your doctor about whether there are preservative free alternatives that would be appropriate for you.

 2018 Mar 3. pii: S1542-0124(17)30311-7. doi: 10.1016/j.jtos.2018.03.002. [Epub ahead of print] 
Exploring topical anti-glaucoma medication effects on the ocular surface in the context of the current understanding of dry eye.
Wong ABC1Wang MTM1Liu K1Prime ZJ1Danesh-Meyer HV1Craig JP2
Abstract
PURPOSE:
To assess tear film parameters, ocular surface characteristics, and dry eye symptomology in patients receiving topical anti-glaucoma medications. 
METHODS:
Thirty-three patients with a diagnosis of open angle glaucoma or ocular hypertension, receiving unilateral topical anti-glaucoma medication for at least 6 months, were recruited in a cross-sectional, investigator-masked, paired-eye comparison study. Tear film parameters, ocular surface characteristics, and dry eye symptomology of treated and fellow eyes were evaluated and compared. 
RESULTS:
The mean ± SD age of the participants was 67 ± 12 years, and the mean ± SD treatment duration was 5.3 ± 4.4 years. Treated eyes had poorer non-invasive tear film break-up time (p = 0.03), tear film osmolarity (p = 0.04), bulbar conjunctival hyperaemia (p = 0.04), eyelid margin abnormality grade (p = 0.01), tear meniscus height (p = 0.03), and anaesthetised Schirmer value (p = 0.04) than fellow eyes. There were no significant differences in dry eye symptomology, meibomian gland assessments, and ocular surface staining between treated and fellow eyes (all p > 0.05) 
CONCLUSIONS:
Adverse changes in tear film stability, tear osmolarity, conjunctival hyperaemia, and eyelid margins were observed in treated eyes. This suggests that inflammatory mechanisms may be implicated in the development of dry eye in patients receiving long term topical anti-glaucoma therapy.

Abstract: "Adolescents with dry eye disease are underserved"

This is a song sheet I can sing from, for sure! We NEVER see dry eye studies about kids!

Participants in this study were Japanese kids aged 10-19. Asians in general, and the Japanese in particular, are known to have higher rates of dry eye than caucasians, and the 21.7% overall prevalence shown in this study is closely similar to the results from another study in a similar age group done ten years ago by one of the participants in the present study - thank you, Dr Ichino!

But I find it very worrying thing is that we actually have nothing to compare these numbers to on this side of the water. We noted this back when the TFOS DEWS II epidemiology team started reviewing existing research way back in 2015 in preparation for the epidemiology report published last year. They can't report on studies that haven't been done! There has been a Korean study published since then - amazing really, on smartphone use. But here? The US is a pretty big consumer of both electronic devices and healthcare - you'd think we would have invested in some information on this one. Sigh. Moving on:

There are two findings here in the abstracts which, to me, were startling and interesting points that may have relevance for other populations:

  • The older girls had worse clinical signs than the boys, but reported fewer symptoms than the boys 
  • Dry eye prevalence and severity among late adolescent girls was comparable to adults

Int J Ophthalmol. 2018 Feb 18;11(2):301-307. doi: 10.18240/ijo.2018.02.20. eCollection 2018.
Gender differences in adolescent dry eye disease: a health problem in girls.
Ayaki M1, Kawashima M1, Uchino M1, Tsubota K1, Negishi K1.
Abstract
AIM:
To evaluate the signs and symptoms of dry eye disease (DED) in adolescents.
METHODS:
This was a cross-sectional, case-control study and outpatients aged 10 to 19y were recruited from six eye clinics of various practices and locations in Japan, and 253 non-DED subjects and 70 DED patients were enrolled. Participants were examined for DED-related signs. Patients were also interviewed to ascertain the presence or absence of six common DED-related symptoms: dryness, irritation, pain, eye fatigue, blurring, and photophobia. Main outcome measures were differences in signs and symptoms of dry eye disease between boys and girls.
RESULTS:
Of the 323 adolescents recruited, 70 (21.7%) were diagnosed with DED. Significant differences between the non-DED and DED groups were found for short tear break-up time (BUT; ≤5s; P=0.000) and superficial punctate keratopathy (SPK; staining score ≥3; P=0.000). Late adolescent girls reported fewer symptoms than late adolescent boys, although their DED-related signs were worse compared to other groups. The prevalence and severity of DED were similar in the Tokyo area compared with suburban and local areas but myopic errors were worse.
CONCLUSION:
We find that adolescents reported symptoms of DED similar to those found in adults, and the majority have short BUT-type DED. The prevalence and severity of DED in late adolescent girls is comparable with adults. Adolescents with DED are underserved and we believe that DED is a hidden but potentially serious health problem for this age group.

Abstract: Sleep deprivation and dry eye and chickens and eggs

This abstract was... depressing. And not just because I really don't enjoy reading about animal testing.

It's that while reading all the ways in which sleep deprivation compromises tear function, I can't help thinking of all those whose sleep deprivation is caused by compromised tear function, whether because they're setting their alarm to get up and add ointment to their eyes to prevent erosions, or the pain factor in general, or the stress from chronic eye pain. Talk about a vicious circle. I guess this is part of why I'm such a fan of taping eyelids down in severe cases.

Lube alone isn't enough. There are many excellent night products - dry eye shields, goggles, masks, and so on that are more convenient and more comfortable. But... when the chips are down and your corneal epithelium is running ragged, tape trumps them all.

Exp Mol Med. 2018 Mar 2;50(3):e451
Sleep deprivation disrupts the lacrimal system and induces dry eye disease.
Li S1,2,3, Ning K1,2,3, Zhou J1,2,3, Guo Y1,2,3, Zhang H1,2,3, Zhu Y1,2,3, Zhang L1,2,3, Jia C1,2,3, Chen Y1,2,3, Sol Reinach P4, Liu Z1,2,3,5, Li W1,2,3,5,6. 
Abstract
Sleep deficiency is a common public health problem associated with many diseases, such as obesity and cardiovascular disease. In this study, we established a sleep deprivation (SD) mouse model using a 'stick over water' method and observed the effect of sleep deficiency on ocular surface health. We found that SD decreased aqueous tear secretion; increased corneal epithelial cell defects, corneal sensitivity, and apoptosis; and induced squamous metaplasia of the corneal epithelium. These pathological changes mimic the typical features of dry eye. However, there was no obvious corneal inflammation and conjunctival goblet cell change after SD for 10 days. Meanwhile, lacrimal gland hypertrophy along with abnormal lipid metabolites, secretory proteins and free amino-acid profiles became apparent as the SD duration increased. Furthermore, the ocular surface changes induced by SD for 10 days were largely reversed after 14 days of rest. We conclude that SD compromises lacrimal system function and induces dry eye. These findings will benefit the clinical diagnosis and treatment of sleep-disorder-related ocular surface diseases.

Abstract: Eye impression-taking materials, what's best?


As an EyePrintPro scleral lens user (going on 4 years now!) this abstract caught my eye. I looked it up to confirm - polyvinylsiloxane is the material used for taking impressions for EyePrintPro  and yes, this study shows it is the better method (less redness, less staining, fewer complications).

This is the stuff I have always affectionately referred to as "high tech blue goo".

Eye Contact Lens. 2018 Feb 28. doi: 10.1097/ICL.0000000000000496. [Epub ahead of print]
Ocular Impression-Taking-Which Material Is Best?
Turner JM1, Purslow C, Murphy PJ.
OBJECTIVES:
To assess the efficacy and effect on clinical signs of a polyvinylsiloxane (Tresident; Shütz Dental Group GmbH, Germany) compared with an irreversible hydrocolloid (Orthoprint; Zhermack SpA, Badia Polesine, Italy) for ocular impression-taking.
METHODS:
Twenty subjects were recruited (13 female and 7 male), with mean age 31.1±4.6 years (SD) (range 25.8-39.7). Subjects attended for 2 sessions, each of 1-hr duration, on 2 separate days. Each session was scheduled at the same time on each day. At each visit, the subject underwent an ocular impression procedure, using either Tresident or Orthoprint, in random order and to one eye only. Investigator 2 was blind to this assignment. Two experienced practitioners conducted the study, investigator 1 performed the ocular impression procedures and investigator 2 observed and assessed the clinical signs: logMAR visual acuity, ocular surface staining, tear break-up time (TBUT), and ocular hyperemia.
RESULTS:
Visual acuity was unaffected by either material; TBUT was marginally disrupted by both materials, but was not clinically significant according to published criteria; ocular redness increased with both materials; and corneal staining was significantly greater after Orthoprint impression. Less redness and clinically insignificant staining after impression-taking, with fewer clinical complications, was found after use of Tresident.
CONCLUSIONS:
Tresident offers a quicker, more effective, and clinically viable method of obtaining ocular impression topography compared with the traditional Orthoprint, and Orthoprint causes significantly more superficial punctuate staining of the corneal epithelium than Tresident.

Abstract: Is cataract surgery the old-but-new LASIK, as regards dry eye?


I think this is the most dramatically worded study I've seen on cataract surgery and dry eye. Way to go Dr Galor! It's definitely making me want to go back and re-read some others to remind myself what the numbers were.

Nothing in this surprises me particularly, but it's really something to see it in print. I'm very pleased to see they used a survey that includes the word burning - that's one of the most common and crippling symptoms for those with severe symptoms, but it is omitted way too often in symptom surveys, as  TFOS DEWS II epidemiology report points out. And I love that the participants are almost all men, who are not the primary dry eye demographic, as it makes the results that much more interesting.

Can't wait to see the complete study. Cornea is still on my Dear Santa list.

  • 95% of participants were men
  • 1/3 of patients have persistent postsurgical pain
  • Prevalence compared with refractive surgery, e.g. LASIK
Cornea. 2017 Dec 7
Epidemiology of Persistent Dry Eye-Like Symptoms After Cataract Surgery.
Iglesias E1, Sajnani R2, Levitt RC3,4,5, Sarantopoulos CD3, Galor A1,6.
Abstract 
PURPOSE:
To evaluate the frequency and risk factors for persistent postsurgical pain (PPP) after cataract surgery, defined as mild or greater dry eye (DE)-like symptoms 6 months after surgery. 
METHODS:
This single-center study included 86 individuals who underwent cataract surgery between June and October 2016 and had DE symptom information available 6 months after surgery. Patients were divided into 2 groups: controls were defined as those without DE symptoms 6 months after surgery (defined by a Dry Eye Questionnaire 5 (DEQ5) score 
RESULTS: 
Mean age of the study population was 71 ± 8.6 years; 95% (n = 82) were men. DE-like symptoms were reported in 32% (n = 27) of individuals 6 months after cataract surgery; 10% (n = 8) reported severe symptoms (DEQ5 ≥12). Patients with DE-like symptoms after cataract extraction also had higher ocular pain scores and specific ocular complaints (ocular burning, sensitivity to wind and light) compared with controls with no symptoms. A diagnosis of nonocular pain increased the risk of DE-like symptoms after cataract surgery (odds ratio 4.4, 95% confidence interval 1.58-12.1, P = 0.005). 
CONCLUSIONS: 
Mild or greater PPP occurred in approximately 1/3 of individuals after cataract surgery. Prevalence of severe PPP is in line with that of refractive surgery, dental implants, and genitourinary procedures.

Abstract: Pollution and the ocular surface

Bit of a summary of what pollution means for dry eye symptoms.

 2018 Mar 3. pii: S1542-0124(17)30224-0. doi: 10.1016/j.jtos.2018.03.001. [Epub ahead of print]

Effects of environment pollution on the ocular surface.

Abstract

The twenty-first century is fraught with dangers like climate change and pollution, which impacts human health and mortality. As levels of pollution increase, respiratory illnesses and cardiovascular ailments become more prevalent. Less understood are the eye-related complaints, which are commonly associated with increasing pollution. Affected people may complain of irritation, redness, foreign body sensation, tearing, and blurring of vision. Sources of pollution are varied, ranging from gases (such as ozone and NO2) and particulate matter produced from traffic, to some other hazards associated with indoor environments. Mechanisms causing ocular surface disease involve toxicity, oxidative stress, and inflammation. Homeostatic mechanisms of the ocular surface may adapt to certain chronic changes in the environment, so affected people may not always be symptomatic. However there are many challenges associated with assessing effects of air pollution on eyes, as pollution is large scale and difficult to control. Persons with chronic allergic or atopic tendencies may have a pre-existing state of heightened mucosal immune response, hence they may have less tolerance for further environmental antigenic stimulation. It is beneficial to identify vulnerable people whose quality of life will be significantly impaired by environmental changes and provide counter measures in the form of protection or treatment. Better technologies in monitoring of pollutants and assessment of the eye will facilitate progress in this field.

Dry eye and scleral lens user tips from readers!

From Elizabeth, about a lid cleansing product making a difference for her severe dry eyes:
Since 2008 I have had severe dry eyes. I have been through many routes and still am living a normal life managing my dry eye symptoms. In the beginning 2 years, I had to wear goggles 24/7 and was in constant pain. One thing that had been if inestimable help is using the ( unfortunately very expensive ) Theratear eye wash product twice a day.  It is a strange product, faintly foamy snd smell is strange but it's a natural product (Tea tree oil?) whose characteristics I wish I could duplicate through home made, as it is $24 and the bottle only lasts 10 days. But it has made a world of difference for me, and when I forgo it even for a day I am in much worse shape. 
From Lynn, about lens wetting drops:
...Let’s keep wishing and hopefully one day (soon) someone will manufacture a preservative-free contact lens drop for scleral lens. 
Before my scleral lens, I  was a piggy-back contact lens wearer and tried using BLINK CONTACTS but it seemed to leave a film over the hard lens.  I’m not giving up on BLINK CONTACTS as I do plan on trying it with my scleral lens. I do like BLINK-N-CLEAN contact lens  eye drops and have no problem using it while wearing my scleral lens. 

From Dave, about how he keeps his eyes protected overnight:
I went back to my eye specialist and told him how i manage my dry eye syndrome ( as shown below ) . He said , you shouldnt have to do that , i know that but its the only thing that works for me 
My nightime regime is  as follows 
BEDTIME 
1. Clean eyes and eye lids with preservative free ' eye wipes ' 
2. Ensure hands are very clean 
3. Apply two small blobs on  Allergan ' Lacri-lube' eye ointment to left index finger 
4. Using my right index finger i put one blob into my eye and gently spread it around covering as much of the cornea as possible 
5. Then grab the eye lashes on the same eye lid and spread / pull this around and over the eye ball to coat the inside surface of the eye lid 
6. Repeat this with the other eye 
7. Apply a reasonable amount of Vaseline ' petroleum jelly ' to each eye where the upper and lower eye lids meet ( this acts like mortar betweens two bricks ) 
8. Next , using a tube of Xailin ' eye gel ' squirt a decent amount up inside each eye lid 
9. Close both eyes to keep the eye gel in position 
10. Gently  massage round the outside of each eye lid with eyes closed over the eye ball 
11.This adds more lubrication inside the closed eye 
12. Lastly , spread more Vaseline petroleum jelly over the entire closed eye socket to keep everything in place 
13, And be careful as you stagger back to the bed , and try not to trip over anything 
Note ... I have found over the last few years that everything i use in my eyes has to be ' Preservative free' or problems and soreness ( extremely red eyes ) occurs very quickly 
Ive been carrying out this long winded procedure since early 2016 and have had a lot of success and some decent nights sleep 
ive have had no more severe eye infections partly due to ensuring lubrication at night which stops any Cornea damage , which in turn can lead to eye infections 
its a real pain in the back side to do , but it has  become part of my life 
Hope this can help someone who reads this