Monday, April 9, 2012

Resurgence of scleral lenses

There's a lot going on out there in scleral-land. Did you know?

For those who don't know what I'm talking about, sclerals are extra-large gas permeable contact lenses. Unlike normal contacts, which, soft or hard, basically drape across the cornea, sclerals vault the cornea entirely and their edges rest on the sclera (white of the eye). They can hold a fluid layer over the cornea.

Sclerals have been around for a long time and while never in common use, historically they've been used mostly to treat keratoconus, a progressive disease where the cornea basically gets lopsided and vision can no longer be corrected with glasses. Sclerals make it possible to improve vision in these challenging situations by providing a sort of artificially regular, smooth, surface comprised of liquid and lens on top of the cornea to help re-focus light entering the eye which would otherwise be hitting the retina in all the wrong places.

In more recent years however, sclerals have started to be used in cases of extreme dry eye. That same fluid layer which fixes optics for people with irregular-shaped corneas can also insulate a cornea which has become extremely vulnerable to the environment around it. So some people suffering severe pain, photophobia and other symptoms have been able to get all-day relief with specially designed scleral lenses.

Boston Foundation for Sight have done the vast majority of pioneering work in this area of dry eye treatment to date, and their success has been beautiful to see. What's just as interesting is that in the past couple of years we've been starting to see a considerably more widespread effort to take commercial scleral lenses and adapt them for severe dry eye treatment.

In conversations with patients on the phone, I've been hearing of people fitted at Mayo (that's sure new - they've never been high on the list of successful dry eye treatment centers), Vanderbilt and other clinics. Today in perusing my Google dry eye newsfeeds I saw several articles on sclerals, some reporting on work done at Loyola University and others on individual optometrists' work.

I say, hurray... keep it up. Kudos to ALL of you doctors and patients pursuing sclerals for dry eye. It is challenging, and frustrating, and I believe largely unprofitable - successes are not nearly so frequent as we'd like, but the individual successes are changing many lives for the better and the aggregate successes are moving the knowledge base forward rapidly.

Abstract: TearLab variability

Clinical Utility of Objective Tests for Dry Eye Disease: Variability Over Time and Implications for Clinical Trials and Disease Management.

To evaluate the efficacy of commonly used biomarkers in dry eye disease management in a longitudinal observational case series study followed by an interventional study in a subset of subjects treated with cyclosporine A (0.05%).

Bilateral tear osmolarity, Schirmer, tear film breakup time (TBUT), staining, meibomian grading, and Ocular Surface Disease Index were measured for a period of 3 consecutive months in participants recruited from a clinic-based population at 2 study sites. Fifty-two subjects completed the study (n = 16 mild/moderate, n = 36 severe; age, 47.1 ± 16.1 years). After the 3-month observation period, severe dry eye patients were prescribed topical cyclosporine A and evaluated for an additional 3 months.

Tear osmolarity (8.7 ± 6.3%) exhibited significantly less variability over a 3-month period than corneal staining (12.2 ± 8.8%, P = 0.040), conjunctival staining (14.8 ± 8.9%, P = 0.002), and meibomian grading (14.3 ± 8.8%, P < 0.0001) across the entire patient population. Osmolarity also demonstrated less variation than TBUT (11.7 ± 9.0%, P = 0.059), Schirmer tests (10.7 ± 9.2%, P = 0.67), and Ocular Surface Disease Index (9.3 ± 7.8%, P = 0.94), although the differences were not significant. Variation in osmolarity was less for mild dry eye patients (5.9 ± 3.1%) than severe dry eye patients (10.0 ± 6.9%, P = 0.038). After treatment, average osmolarity and variability were lowered from 341 ± 18 mOsm/L to 307 ± 8 mOsm/L (P < 0.0001, n = 10). A downward trend in symptoms followed changes in osmolarity, declining from 44 ± 17 mOsm/L to 38 ± 18 mOsm/L (P = 0.35). None of the other signs demonstrated a change after treatment.

Over a 3-month period, tear film osmolarity was found to have the lowest variability among commonly used signs of dry eye disease. Reductions in osmolarity preceded changes in symptoms during therapy.

Cornea. 2012 Apr 3. [Epub ahead of print]
Sullivan BD, Crews LA, Sönmez B, de la Paz MF, Comert E, Charoenrook V, de Araujo AL, Pepose JS, Berg MS, Kosheleff VP, Lemp MA.
*TearLab Corporation, San Diego CA †Department of Ophthalmology, School of Medicine, Ondokuz Mayis University, Samsun, Turkey ‡Centro de Oftalmologia Barraquer, Barcelona, Spain §Pepose Vision Institute, St Louis, MO ¶Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, MO ‖Department of Ophthalmology, Georgetown University, Washington, DC **Department of Ophthalmology, George Washington University, Washington, DC.

Abstract: Smart Plugs

I don't care what this study says, I still say DON'T DO IT. I hate SmartPlugs as you all know. The complications may not be widespread but when they happen they are bad, and since good alternatives to this kind of plug exist, there's just no point exposing yourself. Tempting because they're comfy, but... I hate 'em. Too many people have had to have unnecessary surgery on their eyelids dealing with these stupid plugs going places they were never meant to travel.

Clinical efficacy of the SmartPlug™ in the treatment of primary Sjogren's syndrome with keratoconjunctivitis sicca: one-year follow-up study.

To evaluate the efficacy of a thermo-sensitive punctum plug, (SmartPlug™) in Primary Sjogren's Syndrome (pSS) patients with dry eyes, whose symptoms persist despite preservative-free artificial tear treatment. In this study, 22 Primary Sjögren's Syndrome (pSS), as defined by American-European Consensus Group Classification Criteria. All patients being followed up by Ege University Departments of Rheumatology and Ophthalmology. The patients had positive Schirmer test results ( < 5 mm without anesthesia). SmartPlug™ (Medennium, Irvine, California, USA) was inserted into the inferior lacrimal canaliculi of both eyes. Visual acuity measurements, Schirmer I test measurements, lissamine green staining scores, and tear-film breakup times (BUT) were noted before plug insertion and at the 1st, 6th, and 12th months following the procedure. Minimum follow-up period was 6 months for 19 patients and 12 months for 16 patients. Significant improvements were seen in the Schirmer I test scores (before insertion: 1.98 ± 2.67; 1st month: 5.68 ± 6.69; 6th month: 5.35 ± 5.38; 12th month 6.43 ± 5.14 P = 0.006), tear-film BUT in seconds (before insertion: 4.64 ± 3.7; 1st month: 5.80 ± 2.36; 6th month: 7.53 ± 2.92; 12th month 7.50 ± 2.52, P < 0.0001 ), respectively. Thermodynamic punctum plug insertion only in inferior canaliculus is a simple, effective, and comfortable option for treatment of severe aqueous tear deficiency that cannot be controlled using preservative-free tears.

Rheumatol Int. 2011 Dec;31(12):1567-70. Epub 2010 May 21.
Egrilmez S, Aslan F, Karabulut G, Kabasakal Y, Yagci A.
Department of Ophthalmology, Ege University Medical Faculty, Bornova-Izmir, Turkey.

Abstract: Alternative cyclosporine vehicle?

A novel cyclosporin A aqueous formulation for dry eye treatment: in vitro and in vivo evaluation.

Purpose: The aim of the present study was the in vitro and in vivo evaluation of a novel aqueous formulation based on polymeric micelles for the topical delivery of cyclosporin A (CsA) for dry eye treatment.

Methods: In vitro experiments were carried out on primary rabbit corneal cells, which were characterized by immunocytochemistry using fluorescein-labelled lectin I/isolectin B4 for the endothelial cells and mouse monoclonal antibody to cytokeratin 3+12 for the epithelial ones. Living cells were incubated for 1 hour or 24 hours with a fluorescently labelled micelle formulation and analysed by fluorescence microscopy. In vivo evaluations were done by Schirmer test, osmolarity measurement, CsA kinetics in tears and CsA ocular distribution after topical instillation. A 0.05% CsA micelle formulation was compared to a marketed emulsion (Restasis®).

Results: The in vitro experiments showed the internalisation of micelles in the living cells. The Schirmer test and osmolarity measurements demonstrated that micelles did not alter the ocular surface properties. The evaluation of the tear fluid gave similar CsA kinetics values: AUC = 2339 ± 1032 min*µg/mL and 2321 ± 881.63; Cmax = 478± 111 µg/mL and 451 ± 74; half-life = 36 ± 9 min and 28±9 for the micelle formulation and Restasis®, respectively. The ocular distribution investigation revealed that the novel formulation delivered 1540 ± 400 ng CsA/g tissue to the cornea.

Conclusions: The micelle formulation delivers active CsA into the cornea without evident negative influence on the ocular surface properties. This formulation could be applied for immune-related ocular surface diseases.

Invest Ophthalmol Vis Sci. 2012 Mar 16. [Epub ahead of print]
Di Tommaso C, Valamanesh F, Miller F, Furrer P, Rodriguez-Aller M, Behar-Cohen F, Gurny R, Möller M.
Pharmaceutical technology, University of Geneva, 30 Quai Ansermet, Geneva, 1211, Switzerland.

Abstract: Punctal cautery in GvHD patients

Surgical management of lacrimal punctal cauterization in chronic GVHD-related dry eye with recurrent punctal plug extrusion.

We investigated the efficacy of lacrimal punctal occlusion surgery with a cautery device in patients with chronic GVHD (cGVHD)-related dry eye, with recanalization of puncta and recurrent punctal plug extrusion. A total of 23 puncta from 14 eyes of 10 patients with chronic GVHD (cGVHD)-related dry eye underwent punctual thermal cauterization with a high-temperature disposable cautery device. All patients were refractory to conventional treatment, including artificial tear eye drops, autologous serum eye drops and vitamin A eye drops, and had a history of recanalization and recurrent punctal plug extrusion. The effect of lacrimal punctal cauterization by thermal cautery device was evaluated by changes in subjective symptom scores, corrected distance visual acuity, Schirmer's test values, fluorescein staining scores, rose bengal staining scores, and tear-film break-up time before and 3 months after the surgery. Subjective symptom scores, Schirmer's test values, fluorescein and rose bengal scores, and tear-film break-up time improved significantly 3 months after the surgery. Recanalization of puncta was not observed in all the cases (0 of 14 eyes, 0%). Lacrimal punctal cauterization was effective with no recanalization and significant improvements in subjective symptoms and the ocular surface environment in cGVHD-related dry eye patients who had been refractory to conventional treatments

Bone Marrow Transplant. 2012 Mar 19. doi: 10.1038/bmt.2012.50. [Epub ahead of print]
Yaguchi S, Ogawa Y, Kamoi M, Uchino M, Tatematsu Y, Ban Y, Ohba E, Okamoto S, Goto E, Tsubota K.
Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.

Abstract: Dry eye in severe anorexia nervosa

Ophthalmic changes in severe anorexia nervosa: A case series.

We describe the diagnosis and management of lagophthalmos, or failure of eyelid closure, in five patients with severe anorexia nervosa (AN) who complained of dry, irritated eyes and photophobia.

Five patients with these findings are described retrospectively.

Examination revealed lagopthalmos in the setting of ptosis and enophthalmos, with multiple other starvation-mediated medical complications.

These eye findings, as complications of AN, have not been described in the literature. With careful protective measures, initiation of nutritional rehabilitation, and intensively monitored early refeeding, these patients' ocular abnormalities and associated symptoms resolved completely. Recognition of this pathology and appropriate management can prevent long-term morbidity in the form of permanent loss of visual acuity due to corneal abrasions and improve the outcomes for these patients with severe AN. © 2012 by Wiley Periodicals, Inc. Int J Eat Disord 2012.

Int J Eat Disord. 2012 Mar 12. doi: 10.1002/eat.20970. [Epub ahead of print]
Gaudiani JL, Braverman JM, Mascolo M, Mehler PS.
ACUTE Center for Eating Disorders, Denver Health Medical Center, Denver, Colorado; Department of Medicine, University of Colorado School of Medicine, Denver, Colorado.

Abstract :Latent dry eye disease state variable.

Latent dry eye disease state variable.

Purpose:Evidence is growing that dry eye represents a common disease process resulting from a number of underlying pathologies that impact the ocular surface and that clinical estimates of dry eye severity reflect the magnitude of a single dry eye disease state variable, Θ. A theory for estimating Θ from scaled clinical observations is developed and the hypothesis is tested that Θ exists.

Methods:The theory is developed around three assumptions: 1) a monotonic function unique to each person and indicator maps the indicator onto Θ, 2) between-person differences in mapping functions are random, and 3) observed indicator values include random perturbations. Data recently published by Sullivan and his colleagues were digitized from scatter plots of seven different indicators versus a composite severity score (square root of summed weighted squared indicator scores).

Results:The data were analyzed with a model derived under the specific assumptions that between-person variance in mapping functions is independent of the indicator value and random perturbations in observed indicator values are normally distributed. Tear osmolarity was the most sensitive indicator, tear breakup time was the least. The distribution of residuals (squared difference between observed and predicted indicator values) agreed with model expectations for all indicators except tear osmolarity, which had larger residuals than expected, and the composite severity score, which had smaller residuals than expected.

Conclusions:The results are consistent with the existence of a single latent dry eye disease state variable. Only tear osmolarity does not appear to map monotonically and/or unidimensionally onto the latent variable.

Invest Ophthalmol Vis Sci. 2012 Mar 9. [Epub ahead of print]
Massof RW, McDonnell PJ.
Ophthalmology, Johns Hopkins Univ Sch of Med, 550 N Broadway 6th Floor, 6th Floor, 550 N. Broadway, Baltimore, Maryland, 21205-2020, United States.

Abstract: Lipiflow case report with MG dropout

I guess it's nice to have some hopeful reports like this to round out some of the less impressive results I've been hearing from some of the patients. What we'll all think of it 3 years down the road is anyone's guess at this point.

Case Report: A Successful LipiFlow Treatment of a Single Case of Meibomian Gland Dysfunction and Dropout.

The aim of this study was to investigate whether a single case of meibomian gland dysfunction (MGD), with significant MG dropout resulting in evaporative dry eye, could be effectively treated with the LipiFlow (a new Food and Drug Administration-approved thermodynamic pulsatile treatment).

A 39-year-old white woman experienced severe dry eye symptoms because of MGD with considerable MG dropout resulting in evaporative dry eye. Standardized diagnostic MG expression and meibography led to the tentative diagnosis of nonobvious MGD (only 1 functional MG on each lower lid) and MG dropout (∼50% of the lower lid MGs were missing with the remaining MGs being severely truncated). The patient underwent a single 12-min LipiFlow treatment per eye and returned for follow-up at 1 and 7 months posttreatment.

The LipiFlow treatment increased the number of functional lower lid MGs from 1 to 5 glands OD and 1 to 7 glands OS at 1 month with slight regression at 7 months (4 OD and 4 OS); increased fluorescein break-up time from 4 to 7 sec OD and 4 to 9 sec OS at both 1 and 7 months; and decreased symptom scores by approximately 50% at 1 month and approximately 75% at 7 months.

These results demonstrate the effectiveness of the LipiFlow in restoring MG function and improving ocular comfort even in this particular case of significant MG dropout and MG truncation.

Eye Contact Lens. 2012 Mar 12. [Epub ahead of print]
Korb DR, Blackie CA.
Korb Associates (D.R.K., C.A.B.), Boston, MA; and TearScience Inc. (D.R.K., C.A.B.), Morrisville, NC.

Abstract: Chickens and eggs or... heterogeneous freerange poultry?

Allergic conjunctivitis happens, dry eye happens, sometimes they both happen. This is an interesting abstract reminding us of the substantial overlap in dry eye and allergy symptoms.

Incidentally there was an excellent post by Scout on DryEyeTalk today about the difference between typical airborne allergans and contact allergans.

Allergic conjunctivitis and dry eye syndrome.

Allergic conjunctivitis (AC) and dry eye syndrome (DES) are 2 of the most common anterior inflammatory disorders of the ocular surface and one does not preclude the coexistence of the other.

To examine the potential overlap between AC and DES as comorbidities.

Using the validated questionnaire known as Subjective Evaluation of Symptom of Dryness, we studied self-reported itchiness, dryness, and redness. In an outpatient optometric setting, 689 patients treated from January 1, 2007, to January 1, 2011, were surveyed for their ocular history and categorized according to their reported level of discomfort of itchiness, dryness, and redness.

Patients ranged in age from 5 to 90 years (median age, 25 years; 39.5% male; 60.5% female). In the studied 689 patients, clinically significant itchiness was found in 194 (28.2%), dry eyes in 247 (35.8%), and redness in 194 (28.2%). Symptom overlap was demonstrated in many of the patients. Of the 194 patients with itchiness, 112 (57.7%) had clinically significant dryness. In the 247 patients with dry eyes, 112 (45.3%) had clinically significant itch. Redness was apparent in 120 of the 194 patients with itch (61.9%) and 122 of the 247 patients with dryness (49.4%). Statistical analysis demonstrated that self-reported itchiness, dryness, and redness were not independent of each other (P<.001; Pearson χ(2) test). The odds of patients with "itchy eyes" also experiencing dry eyes were 2.11 times and the odds of these patients also experiencing redness were 7.34 times that of patients with nonitchy eyes.

Most patients with "itchy eyes" consistent with AC also have dry eyes and redness. These results suggest that some symptomatic patients concomitantly have features of AC and DES.

Ann Allergy Asthma Immunol. 2012 Mar;108(3):163-6.
Hom MM, Nguyen AL, Bielory L.