Thursday, November 19, 2009

Abstract: The life and times of... normal meibomian glands

The Diurnal Secretory Characteristics of Individual Meibomian Glands.
Cornea. 2009 Nov 11.[Epub ahead of print]
Blackie CA, Korb DR.
From the *Korb Associates, Boston, MA; and daggerTearScience, Inc, Morrisville, NC.

PURPOSE:: To investigate the diurnal secretory characteristics of individual meibomian glands (MGs).

METHODS:: Ten subjects (4 females and 6 males) with healthy eyelid appearance and without dry eye symptoms were recruited (mean age = 23.8 +/- 1.8 years). Both right and left lower eyelids were marked in 3 places to locate 5 consecutive MGs in each third (temporal, central, and nasal) of the lower eyelid. A total of 15 MGs per eye were diagnostically expressed for 10 seconds on both right and left lower eyelids every 3 hours for 4 consecutive measurements over a 9-hour period.

RESULTS:: Thirty-four percent of all tested MGs yielded liquid secretion at all measurements. Sixty-nine percent of the tested nasal MGs yielded liquid secretion at all measurements in contrast to 31% of the central MGs and only 22% of the temporal MGs. The mean numbers of MGs secreting liquid oil were significantly higher in the nasal section relative to the central and temporal sections at all measurements (p < 0.001, all measurements).

CONCLUSIONS:: (1) A single MG is capable of secreting oil on demand over the course of a working day ( approximately 9 hours); (2) nasal MGs were the most likely to secrete upon demand over the course of day compared with the temporal and to a lesser degree the central MGs; and (3) secretory characteristics of individual MGs examined as a function of their location in the lower eyelid does not change diurnally.

Abstract: KLAL in LSCD

Long-term outcomes of keratolimbal allograft for total limbal stem cell deficiency using combined immunosuppressive agents and correction of ocular surface deficits.
Arch Ophthalmol. 2009 Nov;127(11):1428-34.
Liang L, Sheha H, Tseng SC.

OBJECTIVE: To determine the long-term outcomes of keratolimbal allograft (KLAL).

METHODS: Scores of such risks as infrequent blinking, blink-related microtrauma, conjunctival inflammation, elevated intraocular pressure, dry eye, symblepharon, lagophthalmos, and previous KLAL or penetrating keratoplasty (PKP) failure were calculated and recorded before, during, and after KLAL. Prolonged oral mycophenolate mofetil and tacrolimus and short-term prednisone and acyclovir were administered in 12 eyes (10 consecutive patients) with total limbal stem cell deficiency after KLAL. Ten eyes underwent subsequent PKP.

RESULTS: More corrective measures were required in eyes with higher risk scores. During a follow-up of 61.2 months (standard deviation [SD], 18.2; range, 36-91 months) after KLAL, postoperative epithelial breakdown due to exposure occurred late in the period after PKP and remained a primary risk. Mean daily doses of 1.4 g of mycophenolate mofetil and 1.6 mg of tacrolimus were administered for 52.7 months (SD, 22.5; range, 23-91 months) with few adverse effects and reached trough levels of 1.6 microg/mL (SD, 0.6 microg/mL) and 4.5 ng/mL (SD, 2 ng/mL), respectively. Keratolimbal allograft and PKP rejection was noted in 2 and 3 eyes, respectively, though there was a reversal in 1 eye in each group, yielding final KLAL and PKP survivals in 10 and 8 eyes, respectively, and ambulatory visual acuity of up to 20/20 in 10 eyes for 67.2% of the entire follow-up period.

CONCLUSION: Correction of ocular surface deficits combined with an immunosuppressive regimen further improves the long-term outcome of KLAL in eyes with total limbal stem cell deficiency.

Abstract: Topical naltrexone

Not all that relevant to our crowd (most of us would rather have a decrease rather than increase in corneal sensitivity!) but interesting nonetheless.

Dry eye reversal and corneal sensation restoration with topical naltrexone in diabetes mellitus.
Arch Ophthalmol. 2009 Nov;127(11):1468-73.
Zagon IS, Klocek MS, Sassani JW, McLaughlin PJ.

OBJECTIVE: To determine if topical application of naltrexone hydrochloride (NTX), an opioid antagonist, restores tear production and corneal sensation in rats with diabetes mellitus.

METHODS: Type 1 diabetes was induced with streptozotocin in rats. Tear production was measured by the Schirmer test, and corneal sensitivity, by an esthesiometer. Eye drops of 10(-5)M NTX or sterile vehicle were administered either once only or 4 times a day for 1 or 5 days; a single drop of insulin (1 U) was given once only.

RESULTS: Dry eye and corneal insensitivity were detected in the diabetic rats beginning 5 weeks after streptozotocin injection. One drop of NTX or 4 times a day for 1 or 5 days reestablished tear production and corneal sensitivity within 1 hour of administration. The reversal of dry eye lasted for up to 2 to 3 days depending on drug regimen, but restitution of corneal sensation lasted for 4 to 7 days. Topical application of 1 eye drop of insulin restored corneal sensitivity within 1 hour and lasted for at least 2 days. In contrast, 1 eye drop of insulin did not increase tear production at 1, 24, or 48 hours compared with diabetic animals receiving sterile vehicle.

CONCLUSION: Topical treatment with NTX normalizes tear production and corneal sensitivity in type 1 diabetic rats.

CLINICAL RELEVANCE: Topical application of NTX to the ocular surface may serve as an important strategy for treating dry eye and corneal anesthesia in diabetes. Its effect, if any, in other forms of decreased corneal sensitivity and/or dry eye should be investigated.

Abstract: Stem cell transplantation

Baseline profiles of ocular surface and tear dynamics after allogeneic hematopoietic stem cell transplantation in patients with or without chronic GVHD-related dry eye.
Bone Marrow Transplant. 2009 Nov 9.
Wang Y, Ogawa Y, Dogru M, Tatematsu Y, Uchino M, Kamoi M, Okada N, Okamoto S, Tsubota K.
[1] Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan [2] Department of Ophthalmology, The Eye and ENT Hospital of Fudan University School of Medicine, Shanghai, China.

We evaluated ocular surface alterations in allogeneic hematopoietic stem cell transplantation (HSCT) recipients with or without chronic GVHD-related dry eye in a prospective study. Fifty eyes of 25 post-HSCT patients and 28 eyes of 14 age-matched healthy controls were included. Meibomian gland (MG) obstruction, tear evaporation rate, corneal sensitivity (CS), Schirmer test-I, tear break-up time (BUT) and ocular surface vital staining were examined. Conjunctival impression and brush cytology specimens were collected to evaluate the goblet cell density (GCD) and the inflammatory cell numbers. Obvious MG obstruction, decreased CS and enhanced tear evaporation rate were found in post-HSCT patients compared with normal controls. In addition, decreased conjunctival GCD, increased conjunctival squamous metaplasia and inflammatory cells were noted in cGVHD-related dry eyes compared with normal controls and post-HSCT without dry eye subjects. Furthermore, the conjunctival inflammatory cells were significantly higher in severe dry eyes compared with mild dry eyes (P=0.03). We found comprehensive ocular surface alteration in post-HSCT patients, regardless of whether they had cGVHD-related dry eye or not. The results suggest that the extent of inflammatory process seems to have a pivotal role in the outcome of the cGVHD-related dry eye.

Monday, November 16, 2009

Abstract: Aussie study on McMonnies questionnaire

McMonnies Questionnaire: Enhancing screening for Dry Eye Syndromes using Rasch Analysis.
Invest Ophthalmol Vis Sci. 2009 Nov 5.
Gothwal VK, Pesudovs K, Wright T, McMonnies C.
NH&MRC Centre for Clinical Eye Research, Department of Ophthalmology, Flinders Medical Centre and Flinders University of South Australia, Adelaide, Australia.

PURPOSE: To determine, using Rasch analysis, if the McMonnies questionnaire satisfied the properties of a measure and whether screening for dry eye syndromes (DES) could be enhanced using different scoring approaches.

METHODS: The questionnaire was self-administered by 43 female Sjögren syndrome patients (>45 years) recruited from a specialized rheumatology clinic and 140 age-matched controls. Data were scaled using Rasch analysis and assessed for response category behavior and ability to reliably discriminate between severity of participant's dry eye symptoms (i.e. person separation reliability; minimum acceptable value 0.80). Standard summary statistics of screening performance were calculated for raw and Rasch-scaled scores from Receiver-Operating Characteristic analysis including area under the curve (AUC). Best predictors (i.e. questions) from a discriminant analysis were used to calculate a discriminant function for both Rasch-scaled and raw scores.

RESULTS: Response categories were not used as intended, necessitating collapse of categories. Person separation reliability was inadequate (0.75). Rasch-scaled discriminant cut-off score of -2.29 logits from 7 items provided an AUC of 0.99 with 95% sensitivity. However, discriminant raw score from modification in the scoring of a question, i.e. use of medications (used singly rather than individual questions) provided AUC (0.97) not significantly different (z = 1.11, p = 0.27) with 98% sensitivity and required only 2 questions.

CONCLUSIONS: In this population, the McMonnies questionnaire does not function as a measure. However, various scoring methods can be used to efficiently screen for DES.