Tuesday, March 20, 2018

Ouch: Another study of persistent dry eye after cataract surgery

Who is most likely to get dry eye after cataract surgery?

In this study, they looked at patients who underwent cataract surgery. If their OSDI scores were greater than 12 three months after surgery, they deemed them as having persistent dry eye symptoms.  The point of the study was to analyze what was different about those patients at the time of surgery and soon after: is it possible to predict who will have persistent dry eye after cataract surgery?

One-third (31 of 96) of the patients had persistent dry eye symptoms after cataract surgery. Ouch!

Risk factors were determined to be:
  • High OSDI scores before surgery
  • Low TBUT 1 month after surgery
  • Low MG orifice obstruction score
  • Increased MG dropout
In other words, if they were symptomatic before cataract surgery, and/or if they had meibomian gland issues. 

Eye doctors need to be screening cataract patients for dry eye, advising them on risks and advising them on treatments for dry eye prior to cataract surgery.

Perioperative Ocular Parameters Associated With Persistent Dry Eye Symptoms After Cataract Surgery.
Cornea. 2018 Mar 14. doi: 10.1097/ICO.0000000000001572. [Epub ahead of print]
Choi YJ1, Park SY, Jun I, Choi M, Seo KY, Kim EK, Kim TI.
To evaluate perioperative dry eye (DE) syndrome and meibomian gland dysfunction (MGD) parameters associated with persistent DE symptoms after cataract surgery.
We enrolled patients who underwent uncomplicated cataract surgery without previous ocular comorbidities and previous use of ophthalmic treatment except for artificial tears at a single tertiary hospital. Lipid layer thickness, meibomian gland (MG) dropout, tear breakup time, Oxford staining score, lid margin abnormality, meibum quality, meibum expressibility, MG orifice obstruction, MGD stage, Ocular Surface Disease Index (OSDI), and Schirmer test score were prospectively assessed in order at baseline and 1 and 3 months postoperative. Patients with an OSDI score >12 at 3 months postoperative were defined as patients with persistent DE symptoms after cataract surgery. Multivariate logistic regression was then used to determine risk factors for persistent DE symptoms.
A total of 116 eyes of 116 patients were enrolled, and 96 patients completed all examinations until 3 months postoperative. Thirty-one patients had persistent DE symptoms at 3 months postoperative. The Oxford staining score, lid margin abnormality, meibum quality, and MGD stage were improved over time. Baseline high OSDI scores [odds ratio (OR), 1.072; P = 0.001] and 1 month postoperative low tear breakup time, low MG orifice obstruction scores, and increased MG dropout (OR, 0.322; P < 0.001, OR, 0.291; P = 0.015, OR, 1.145; P = 0.007, respectively) were determined as risk factors for persistent DE symptoms after cataract surgery.
Ocular parameters at baseline and at 1 month postoperative were important in predicting persistent DE symptoms after cataract surgery.

Sunday, March 11, 2018

Abstract: High success rates for scleral lenses in graft-v-host-disease patients

These numbers are unsurprising to anyone who knows people with severe chronic GvHD (when they develop severe dry eye, among other things, following a bone marrow transplant for example), but nonetheless impressive:

  • 97% of patients had improvement in quality of life
  • 92% of patients continued to use sclerals (mean follow-up time was more than 1.5 years)
  • Corneal damage, vision and quality of life were all assessed 2 months after starting and all improved

Bone Marrow Transplant. 2017 Jun;52(6):878-882. doi: 10.1038/bmt.2017.9. Epub 2017 Feb 20.
Scleral lenses for severe chronic GvHD-related keratoconjunctivitis sicca: a retrospective study by the SFGM-TC.
Magro L1,2, Gauthier J1,2, Richet M3, Robin M4, Nguyen S5, Suarez F6, Dalle JH7, Fagot T8, Huynh A9, Rubio MT10, Oumadely R11, Vigouroux S8, Milpied N8, Delcampe A12, Yakoub-Agha I1,2,13.
Author information
Chronic GvHD-related keratoconjunctivitis sicca (cGvHD-related KCS) can significantly alter the quality of life of patients after allogeneic hematopoietic stem cell transplantation. The aim of this work was to assess the efficacy and tolerability of scleral lenses to treat severe cGvHD-related KCS. In this retrospective, multicenter study, we included 60 consecutive patients diagnosed with cGvHD-related KCS and fitted with scleral lenses. Patients were evaluated at baseline and at 2 months with the following tests: the Ocular Surface Disease Index (OSDI) to assess quality of life, the Oxford score to grade corneal damage and the logarithm of minimal angle of resolution (Log MAR) scale to determine visual acuity. We observed improvement in quality of life in 58 patients (97%). All parameters improved at 2 months. We observed significant differences at 2 months compared with baseline for the mean OSDI (86 versus 30, respectively, P<0 .001="" 0.10="" 0.33="" 1.3="" 2-125="" 20.5="" 5="" a="" acuity="" and="" as="" blockquote="" cgvhd-related="" discontinued="" efficient="" follow-up="" in="" kcs.="" lenses="" mar="" mean="" median="" months="" of="" og="" only="" oxford="" p="" patients="" range:="" respectively="" scleral="" score="" severe="" the="" tolerated="" treatment="" versus="" very="" visual="" was="" well="" were="" with="">

Abstract: Case reports of Cacicol use in Sjogrens patients with superficial ulcerative keratitis

Interesting case report on some folks with severe corneal disease. They clearly had to stay on it to get any kind of continued benefits, but those benefits sound pretty dramatic:
  • decreased pain, burning, irritation and FBS
  • improved vision
  • healing of diffuse keratitis (after several months treatment)

Medicine (Baltimore). 2018 Mar;97(10):e9935.
Evaluation of a new matrix regenerating agent in patients with Sjögren syndrome and superficial ulcerative keratitis resistant to conventional therapy: A report of 3 cases.
Fajnkuchen F1,2, Barritault D3, Giocanti-Aurégan A1,4. 
Sjögren syndrome (SS) is frequently associated with ulcerative keratitis, which is difficult to treat due to lacrimal tear deficiency and inflammation of the ocular surface. 
We report the successful additive effect of a matrix regenerating agent (RGTA, Cacicol) in SS patients with severe superficial ulcerative keratitis resistant to conventional therapy. 
Retrospective, noncomparative case series of patients with primary or secondary SS associated with chronic diffuse keratitis. 
All patients (3 women, aged 46, 59, and 84 years) had several years of dry-eye disease history and recurrent keratitis despite having used maximal dose topical therapies including artificial tear substitutes, topical vitamin A, and cyclosporine 0.05% emulsion. All patients suffered from dry, diffuse, and chronic superficial keratitis of at least 75% of the corneal surface, with no sign of corneal neovascularization or opacity. 
RGTA treatment led to a rapid and marked decrease of ocular pain, burning, irritation, foreign body sensation, and improvement of visual acuity. Total diffuse keratitis healing occurred after several months of treatment. Discontinuation of RGTA administration led to the recurrence of severe keratitis; re-introduction of RGTA was successful. No local or systemic adverse effects related to treatment were reported. 
RGTA treatment was effective and safe in this small series of 3 patients suffering from SS associated with recurrent or chronic superficial ulcerative keratitis resistant to conventional therapy.

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
To assess tear film parameters, ocular surface characteristics, and dry eye symptomology in patients receiving topical anti-glaucoma medications. 
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. 
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) 
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.
To evaluate the signs and symptoms of dry eye disease (DED) in adolescents.
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.
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.
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. 
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.
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.
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.
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.
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.
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. 
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 
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). 
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.


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 
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 

Monday, February 26, 2018

Tear film osmolarity with ocular allergy

This study was just looking at the effect of artificial tears on tear film osmolarity in ocular allergy patients. They measured OSDI symptom scores and clinical signs including tear osmolarity, TBUT and Schirmer 1.

Nothing special here but it caught my eye because the best results were with Thera Tears were the best in the group (they don't say by how much) and Thera Tears, while perhaps not so popular these days, was the drop developed by Jeff Gilbard, an important pioneer in the dry eye world who championed a better understanding of the role of tear film osmolarity. Dr Gilbard also played a prominent role in educating about nutritional supplements for dry eye.

 2018 Mar-Apr;32(2):403-408.
Tear Film Osmolarity in Subjects with Acute Allergic Rhinoconjunctivitis.
Nitoda E1Lavaris A1Laios K1Androudi S2Kalogeropoulos CD3Tsatsos M4Damaskos C5,6Garmpis N5,6Moschos MM7.

Acute allergic rhinoconjuctivitis is the most common form of ocular allergies. The pathogenetic mechanisms are based on an immunoglobulin E (IgE)-mediated hypersensitivity reaction. On the other hand, tear osmolarity has been suggested to be an index of ocular surface damage and inflammation. These data were the motive to investigate the levels of tear osmolarity in subjects with acute allergic rhinoconjuctivitis, before and after administration of artificial tears.
Forty-five subjects with acute allergic rhinoconjuctivitis were randomly divided into three groups, based on the type of artificial tears that they received: Group A (Thera tears), Group B (Wet therapy) and Group C (Tears Naturale free). The eye drops were administered six times a day for 60 days and all subjects underwent grading of subjective symptoms and clinical examination at baseline and at the end of the treatment. 
The diagnosis of severe eye disease, which was based on ocular surface disease index (OSDI; Allergan, Inc, Irvine, CA, USA) and tear osmolarity values, concerned all patients at baseline. Although the administration of artificial tears significantly ameliorated the symptoms and the ocular variables in all groups, the results were better in the first group. Tear osmolarity was strongly and negatively correlated with tear film breakup time (BUT) and Schirmer I test at 2 months. Contrariwise, symptoms were eliminated, when tear osmolarity was decreased. 
Acute allergic rhinoconjuctivitis is characterized by tear hyperosmolarity, which can be rehabilitated with the administration of hypotonic artificial tears.

Monday, February 19, 2018

As a layperson, how do you deconstruct an artificial tear study? (PART 1)

All about a study abstract

At the bottom of this page, I've posted the abstract of a study that was just published a few days ago, which compares three artificial tears and their effect on the "signs, symptoms and inflammatory status" of the patients in the study.

I've spent years looking at abstracts, often digging into the complete studies to the extent they are available online for free, and trying to distill the content into fact bites and language normal people can understand.

I almost always skip the artificial tear ones or "blurbify" them as the meaningless repeats they so often seem to be. This one, though, prompted me to start asking more questions. Somewhere in the process, I reverted to musing on how inaccessible some of these studies are to the casual reader who just wants to know one thing: what works?

So I decided to take the opportunity to pick one apart and lay out all the gory details. I thought it wouldn't take long. I was wrong. Just figuring out which drops were being studied made this a very long blog post, so I'm turning this into a mini-series, because the same study has much, much food for thought and discussion.

PART 1. What are they talking about?

You'd think the products or drugs being studied would be obvious.

Sort of?

Absolutely not.

Study abstracts usually don't reference brand names. For example, studies about Restasis or Xiidra will refer to them as "cyclosporine ophthalmic emulsion 0.05%" and "lifitegrast ophthalmic solution 5%". The brand names don't go in the keywords either, incidentally, so if you're trying to do a broad search, you kind of need to know what you're doing.

So, we have to do a little legwork to figure out which the three products in this study are.

We are told they are:
  1. carboxymethylcellulose-glycerine-castor oil (CGC)
  2. carboxymethylcellulose (CMC)
  3. hydroxypropyl guar (HPG)
Having read a great many of these abstracts over the years, I recognize the pattern:
We are watching a really cheesy stage portrayal of scene CCXLIV of Shakespeare's classic work, "Refresh and Systane". In this scene, the young, vigorous, ambitious scion of the Refresh family uses a blunted sword on stage to disable his elder brother before moving on to inflict would-be fatal wounds in the oldest, tiredest member of the Systane family and, seeing him duly fall to the ground clutching his heart, gloats at his success. 

Alas, no. It's just because I've seen this play out so many times. Now I peek ahead to the conclusion paragraph and realize I could not be more wrong, at least as regards the plot. In fact.... Oooooh. This one might actually be ever so slightly fun and interesting (to nerds like me).

But I'm getting ahead of myself. Back to the homework on the products.

Who ARE these three masked actors, really?

We know they are all artificial tears, a/k/a "tear supplements". Actually, that term may be a little confusing to the layperson because there are so many superfluous nutritional supplements sold to improve tears - and so many dime-a-dozen studies published about them - that it wouldn't be surprising if that's where your head goes the moment you see the word "supplement". (I freely admit mine did, at first glance, and I read these things all the time!) But as soon as you get to the ingredients, it's clear we're not talking about another Omega 3 study. Back up. Oh, yes, tear supplements = artificial tears = "lubricant eye drops", etc.

That should make it very easy to find the products, right? After all, I have a handy ingredient reference list posted at the Dry Eye Shop for all the major brands of artificial tears and even a few minors. However, as always, I'm making a mental note even before I start that we'll have to make some assumptions as we match them up. On the one hand, they could be the major brands, and almost certainly are. I mean, who else but Allergan puts money into studying artificial tears? But if they aren't, we can't assume the results will apply to the name brands. The only things listed in the abstract are the polymer and lipid type ingredients. The abstract doesn't list the concentrations (which are listed on product packaging), let alone any more minor differences, and we certainly don't know what might be lurking in the inactive ingredients.

Sidebar: Speaking of inactive ingredients, and noting castor oil in one drop: because of the archaic and arcane way the FDA regulates artificial tears, if there is castor oil present, you can bet it's listed in the inactives, because it's not allowed to be listed in the actives! Go figure!

So anyway, I'm thinking this will be easy. Then I look them up.

QUESTION #1: What is the drop referred to as"carboxymethylcellulose-glycerine-castor oil"?

Refresh Optive Advanced is the first one on my list that has all three of these ingredients - the first two are listed in actives, the third in inactives, as I said. But it also has polysorbate 80 listed in the actives. So are we talking about a different drop, or do the authors just not care about the polysorbate 80? Furthermore, Refresh Optive Advanced Mega 3 also contains all three of these ingredients; the active ingredients are identical; but Mega 3 also contains more lipids, also listed in the inactives where the FDA regs force them to dwell.
ANSWER: Probably Refresh Optive Advanced? Maybe Refresh Optive Advanced Mega 3? Maybe something different, but what? Mental note that I really have to find out.

QUESTION #2: What is the drop referred to as "carboxymethylcellulose"?

OK this one could be Refresh, or Refresh Plus, or Theratears, or any number of generics. Unfortunately the abstract does not even bother to specify whether they are preserved or preservative free, let alone the polymer concentration. Mental note that the ambiguities may be deliberate - this is obviously just meant to be the middle of the road ubiquitous artificial tear, right?
ANSWER: I really couldn't care less, but probably Refresh Plus.

QUESTION #3: What is the drop referred to as "hydroxypropyl guar"?

Easy peasy. Systane. They are the only major brand using this ingredient. 

Except... HP is in ALL Systane products. So, is this Systane, or is it Systane Balance (which contains a lipid), or is it Systane Ultra (which is a high concentration), or is it Systane Sport? 

Then I read a little more carefully - the abstract says that CGC and HPG are "emulsified lipids", and Systane Balance is the only emulsion drop in the Systane brand, so this pretty much has to be Systane Balance, unless there's a new knockoff somewhere, but then, knockoffs don't spend money conducting studies.

BUT... FOR HEAVEN'S SAKES! Would the real artificial tear please stand up? By this time I'm fuming over the fact that I probably can't find out without forking over $30 to get a copy of the study or hitting up an academic friend to hunt it down at their university, because I seriously doubt that even any of my ophthalmologist friends subscribe to Cytokine, of all the obscure journals! Not to mention that no one really cares all that much about artificial tear studies anyway, so how many people looking at the abstract would have any more doubts than I did that it's really just another round in the Refresh v Systane challenge, and make an assumption about which specific ones? Yawn, move on. 

As a last resort, I google the study, in case it's one of the ones that really IS available online in full text.

Bingo. There it is, in all its glory! Yes, of course it's Refresh v Systane, but I am still in for some surprises.

#1 = "Optive Plus", by Allergan

Optive WHAT?

Oh. I realize for the first time that the study was done in the UK. Optive Plus is sold on prescription in the UK, AND as far as I can tell, considering they don't list the inactive ingredients, it's at least quite close to if not exactly the preserved version of Refresh Optive Advanced. Kinda called it.

#2 = "Refresh Contacts", by Allergan

Seriously? The UK version looks to be identical with the US one, but... but... but... I thought this was a study of tear supplements, not lens wetting drops?

Then I have a look through Allergan's UK product offerings and I see that they do not, in fact, have a CMC drop other than their contact lens one - which, let's be honest, in the US Refresh Contacts is the same thing as Refresh Tears under a different label anyway right? So it really doesn't matter. Fair enough. It's the sweetly smelling ubiquitous preserved CMC artificial tear under any other name. Called it.

#3 = Systane Balance, by Alcon

Called it.

So now we know WHAT they are talking about.

We have several more questions to go, including:

  • What did they find out, and how?
  • Who cares (if anyone), and why?

I really don't usually have this much fun on Mondays. Thank goodness for the Presidents Day holiday.


 2018 Feb 13;105:37-44. doi: 10.1016/j.cyto.2018.02.009. [Epub ahead of print]

Effect of tear supplements on signs, symptoms and inflammatory markers in dry eye.



Three tear supplements were compared for their effects on the signs, symptoms and inflammatory status of subjects with dry eye disease. Assessments were made before and after both 2 and 4 weeks of treatment.


In this masked, randomized, 3-way crossover trial, eighteen dry eye subjects were recruited. At each visit, symptoms, tear evaporation rate, stability and osmolarity were measured and tear samples were analyzed for 7 inflammatory markers, using multiplex immunoassays. The 3 treatments included carboxymethylcellulose-glycerine-castor oil (CGC), carboxymethylcellulose (CMC) and hydroxypropyl guar (HPG). The CGC and HPG drops are emulsified lipids; CGC also contains osmoprotectants. The CMC drop is a standard aqueous polymeric supplement.


Significant improvements were seen in symptoms (OSDI) and tear stability (NITBUT) with all 3 treatments at 4 weeks. At 4 weeks post-CGC, 6 out of 7 biomarkers demonstrated a >25% reduction (in 40% of subjects). The same reduction (>25%) was seen in 10% of the subjects for CMC and in none of the subjects for HPG. No significantly different change to either evaporation rate or tear osmolarity was found following any of the three treatments.


In this study, the CGC treatment resulted in the greatest reduction in ocular biomarkers of inflammation, while all 3 treatments reduced symptoms and improved tear stability. These results indicate that subject-perceived symptomatic improvements are not necessarily associated with a reduction in objective measures of inflammation.

Humidifiers... in homes using liquid propane

A reader shares his story of noticing a change in their LP gas range's burner flame, and all the detective work he put in to figuring out why - and how it relates to humidifier use.

This is not a subject area I know anything about personally, and it was fascinating to me. We use LP for both cooker and fridge in our tinyhome, but then, we're off grid and don't have a humidifier, so I wouldn't have guessed.

Don't know if you'll remember me but we corresponded a bit a few years ago. As a dry eye sufferer I am a big fan of the work you do to educate folks suffering from dry eyes and I read your newsletter eagerly each time it arrives. 
I recently ran across some info I think might prove useful to your readers and I am writing you today in hopes that you might share it with them. After several, years of being under great control my Sjogrens disease related dry eye symptoms recently began to flare again. It has been a very cold winter here in Maine with attendent increase in the need for home heating which of course creates a very dry inside climate. Thinking that my trusty old humidifier might help I dug it out, filled it with tap water and turned it on.

Sure enough within a few days my dry eye symptoms began to slowly improve and I am actually now able to get some decent sleep.

Alas, shortly after I began using my humidifier my wife began complaining that the burner flame on our LP Gas range began to turn yellow. I checked and sure enough what had been a bright blue flame now appeared a reddish yellow. I did a little checking on the Internet and discovered that the usual cause of a yellow flame was either gas contaminated with water, or an improperly adjusted gas/air mixture. I called my LP Gas supplier who felt that it might have something to do with the LP Gas tank being low and he sent over a truck to fill it.

Sadly this did nothing to cure the problem and the gas company suggested I contact a heating contractor to schedule a maintenance check.

Given that this was going to cost me several hundred dollars, and given that I was looking for an excuse to stop working on my income taxes 😤 I fired up my iPad and did some more research on the yellow flame problem.

Eventually I ran into a YouTube video that proved that running a humidifier in the house would cause a gas range flame to turn yellow! Some folks thought it was because of the moisture added to the air, others felt it had to do with various other factors. Eventually a chemist got involved and he said that sodium was being relased from the water molecules and causing the flame to turn yellow. Someone suggested that using distilled water which is mineral free might cure the problem.

Sure enough I refilled my humidifier with distilled water and within a short time the burner flame changed back to a deep blue color.

Dozens of folks reported having spent hundreds of dollars trying to solve this problem as a yellow flame caused by an incorrect gas/air can result in excessive carbon monoxide production which can prove deadly. Time after time even factory trained representatives were totally unable to correct the problem. And then along came a clever guy...

It is still not entirely clear if the yellow flame created by using tap water in a humidifier creates a carbon monoxide risk but the general consensus is that it does not. I personally have experienced no ill effects normally associated with carbon monoxide but based upon one night's experience it "seems" like using distilled water in my humidifier resulted in a noticeable improvement in my dry eye symptoms. Given that sodium is the major mineral associated with salt, and given that salt is known to have a drying effect it may well be that distilled water is the better choice. So I am going to give it a try...

Might be worth running a short piece on this in your newsletter as I know many dry eye folks use humidifiers.

All Best & Keep Up The Good Work!
Winston Shaw
Just a few notes of my own to add:

  • If you're using LP in your home, I sure hope you have a carbon monoxide detector with fresh batteries! 
  • Cleaning your humidifier regularly is a very important safety tip as well.
  • Ultrasonic humidifiers should be used only with distilled water in any case, as otherwise you can get the "white dust" effect.
  • The EPA says, for mold prevention, you should not let the relative humidity level get above 60% in your home, and ideally, keep it between 30% and 50%. 

Thursday, February 15, 2018

NKCF Family Symposium 2/10/18

Last Saturday, the National Keratoconus Foundation hosted its 2018 Keratoconus Family Symposium at UC Irvine. I had the pleasure of attending and even the privilege of speaking at it.

A bit of background for dry eye readers

For those who have never heard of it: keratoconus is a rare corneal disease affecting at least 1 in 2,000 people (though one of the speakers at the event voiced his opinion that it's actually much more common but frequently goes undiagnosed). I'll borrow directly from the NKFC website for a definition:

Keratoconus, often abbreviated to “KC”,

is a non-inflammatory eye condition in which the normally round dome-shaped cornea progressively thins causing a cone-like bulge to develop. This results in significant visual impairment.

This is obviously not a Dry Eye Thing, so a brief word about how and why I got involved is probably in order. Of course, many keratoconus patients have dry eye, so I have known many over the years just in the normal course of Dry Eye Company 'business' whether through blogging, emails and conversations, or actual retail.

But the closer connection for me with keratoconus patients is through scleral lenses, which are commonly used for correcting the vision impairments keratoconus can cause. (I too have vision not correctible with other types of lenses though for different reasons.) Actually, I first came across keratoconus way back in 2002 or so when I was doing advocacy work for people with complications from LASIK, because there is a medically induced version of keratoconus which we tended to refer to as post LASIK corneal ectasia. These days, because the Dry Eye Shop has expanded more and more into scleral lens supplies, questions that flow in through the shop are the main way I keep up a lot of communication with keratoconus patients, as well as our Facebook group, My Big Fat Scleral Lens, and it's through scleral lenses that I came to know the current director of NKFC, Mary Prudden, who was responsible for organizing this excellent event.

So, on to the actual contents of the day:

Gloria Chiu OD (USC-Roski Eye) provided an excellent framework for the presentations of the day by giving an introduction to keratoconus with an overview of its causes, onset, and progression as well as the treatments, which are pretty much limited to specialty contacts and corneal transplants, though corneal crosslinking is now being used as a preventive treatment for younger cases. If I'm not mistaken, Dr. Chiu is the only PROSE fitter west of the Mississippi. It was a joy to meet her for the first time as I've known a great many of her patients over the years.

Mindy Hutchinson MD (Vita Behavioral Health, PA) talked about the mental health impact of eye disorders. She was diagnosed at the age of 26 with keratoconus, of which she had never heard during medical school. She walked us through her own path and discussed anxiety, depression, learned helplessness and what it looks like to take back control, including education, accommodation, advocacy, and self-care. 

Vivian Shibayama OD (UCLA-Jules Stein) presented on contact lens options for different stages of keratoconus, including: soft torics; corneal RGPs; topography guided RGP designs; piggybacking; hybrid lenses; and finally sclerals. She addressed some practical questions such as about refilling lenses during the day. In a second presentation, she covered scleral lenses in more detail including multifocal optics, EyePrintPro molded lenses, Hydra PEG coating, and various questions relating to solutions for both soft and rigid lenses.

Incidentally, I was curious about the current status of piggybacking - that's something I tried back around 2003 but was not able to tolerate the soft lenses. I wondered whether scleral lenses have made piggybacking obsolete but clearly they haven't - the cost and commitment factors in sclerals are such that the simpler, more cost-effective approach of piggybacking is better for some users who are still able to tolerate lenses on the cornea.

Yours truly presented on practical pointers for scleral lens users including those with dry eye, but you've heard so much from me I won't regurgitate it here!

Marjan Farid MD (UC-Irvine/Gavin Herbert) presented on corneal transplantation techniques. She discussed some current challenges such as rapid visual recovery, astigmatism management and getting patients out of contacts, and improvements in targeting different procedures to specific diseases. Femtosecond laser technology is bringing great improvements due to precisely targeted cuts and she presented on this area in great detail, particularly the zigzag method, including videos of DALK employing femtosecond zigzag cuts on the donor cornea and the receiving cornea. Questions she addressed included: "Does crosslinking ever lead to transplants?" (hopefully infrequently), "Can you get KC after the transplant?" (transplant is only 8-9mm so there is less risk of ectasia), and "How often are sclerals still required after transplant" (fit is better after, so "a lot" don't need sclerals).

Sam Garg MD (UC-Irvine, Gavin Herbert) presented on the hottest topic of the day: corneal cross-linking (CXL), which was finally FDA approved just over a year ago after having been used in Europe for many years. He started with some broader keratoconus background including risk factors (incl. Down syndrome, genetics, eye rubbing, connective tissue disorders) and also mentioned - new to me! - that the cornea is the driest tissue in the body! He explained that, like so many medical interventions, we don't know how crosslinking works, we only know that it seems to be effective at stiffening the cornea. He presented a great deal of technical background on the treatment and how it is employed. It is only approved for patients 14 years old and older. Candidates are those with keratoconus or post LASIK ectasia that is demonstrated to be progressive (though he said that with the younger ages they do not necessarily bother documenting progression first as it can be assumed to be progressive in young patients). He discussed what the procedure and healing period are like and mentioned potential complications such as haze and sterile infiltrates. There is debate about "epi-on vs. epi-off", that is, whether to perform it with or without the corneal epithelium in place. Dr. Garg addressed many audience questions, including: "When does KC historically stabilize?" (it's a spectrum), "How soon is a CXL patient able to wear contacts" (2-3 months or more), "Can it be done on younger than age 14" (off-label, yes), "Will there be any insurance coverage" (Avedro is pushing hard for this), "How much does it cost" ($5-6k with current riboflavin costs), and "How and when is patient satisfaction measured" (this question from yours truly and the answer is that there has been no formal measure of it).

Elio Spinello PhD (CSUN-Northridge) presented on various pitfalls of medical information on the internet, focusing on a variety of tests and red flags to look for when trying to determine the reliability of a given source. He emphasized the importance of having medical providers you trust and presented data on the role this plays in the extent to which people rely on what they read.

Wendy Pawling (UC-Irvine voc. rehab consultant) presented on accommodations in the workplace as well as school environments. She discussed relevant Federal and California disability laws with the aim of informing and equipping people with visual disabilities (assuming they are able to perform their essential job functions) to be able to request accommodations and to know what to expect and what an employer is, and is not, obliged to do. She discussed the interactive nature of the process and privacy limitations; for example, employers are not allowed to ask you your diagnosis, nor can they contact your doctor(s). She gave examples of accommodations she's familiar with at UCI, from equipment or software to modified work schedules.

Rachel Dungan MSSP (NKCF patient advocate) wrapped up the presentations with a powerful, moving talk including her personal story. She shared how keratoconus progressively and profoundly impacted her education and professional trajectory as well as her mental wellbeing for some years before she was diagnosed, and the many ways in which the experience as a whole has changed her. She discussed what patient advocacy and patient empowerment look like, how patients can educate themselves as well as those close to them about their needs both in visual health and emotional health. She described hopeful signs that patient-centered care is being increasingly valued.

The presentations were followed by a tour of the Eye Bank at Gavin Herbert Eye Institute as well as workshops on stress management, advocacy and scleral lens and dry eye troubleshooting. Somewhere in there we also had lunch. Aidan (assistant, who accompanied me to the event) and I sat with a family whose 17 year old son was recently diagnosed. The conversations with the parents were probably the most impactful part of the education I received that day, as they told what it's really like trying to help a young person at such an intensely vulnerable time of life come to grips with having a rare eye disease, as well as the many practical and financial considerations impacting their whole family.

Many thanks to Mary Prudder and NKCF for this wonderful event! I learned so much, and met a lot of wonderful people. It was a great day. - Also, thank you to Aidan for taking great notes for me so that I could just sit back and listen and absorb.