Editor’s note: This volume covers the topics of dry eye disease, infectious
keratitis, glaucoma and the contact lens control of myopia progression.
The hope is that this augments your education, clinical practice acumen
and keeps you up-to-date on important topics concerning contact
lenses and the anterior segment. We are striving to present, in a
succinct and pithy format, important information that does not cut into
your already busy schedule, delivering clinical nuggets for the benefit
of all of your patients.
Ocular Surface Inflammation and Infection
Pham M, Chow C, Badawi D, Tu EY. Use of Infliximab in the
Treatment of Peripheral Ulverative Keratitis in Crohn Disease. Am
J Ophthalmol 152(2):183–188, 2011.
Crohn disease is an inflammatory bowel disease that exhibits
ocular manifestation in approximately 10% of patients. Three
individuals with Crohn-associated peripheral ulcerative keratitis
(PUK), unresponsive to traditional immunosuppressive medication
(i.e., oral prednisone and/or cyclophosphamide) were treated via intravenous infusion of infliximab (Remicade), an anti-TNF-α infusion medication. All patients experienced reduced pain, resolution of inflammation and arrested corneal thinning. Visual acuity improved or remained stable in more than 83% of affected eyes, and similar results were observed upon repeat dosing during recurrences. The authors do caution that before starting patients on this medication, a careful tuberculosis screening must be undertaken since the use of the drug has been associated with new and reactivated cases of tuberculosis. At the moment, although the effects of long-term therapy remain unknown,infliximab appears to produce rapid suppression of sequelae associated with intractable Crohn-associated ulcerative keratitis.Topical 1% voriconazole matches the efficacy of 5% natamycin in the treatment of fungal corneal ulcers, according to researchers at the Maulana Azad Medical College in New Delhi, India. In a study of 30 patients with confirmed fungal corneal ulcers, 100% achieved complete healing when treated with conventional topical natamycin, versus 93% with topical voriconazole.Although eyes treated with voriconazole took slightly longer to resolve (27.4 vs. 24.3 days), the difference was deemed insignificant. Final best-corrected visual acuity, as well as size and depth of residual scarring, were comparable in both treatment groups. Although topical voriconazole
was found to be as safe and effective as natamycin, the authors believe that there is no added advantage to its use,
and that it may have limited potential as a primary therapy due to its reduced shelf life (2–3 days), high cost and
variable bioavailability. Tacrolimus (an immunomodulatory agent) has been considered an alternative treatment of vernal kerato-conjunctivitis (VKC) in children and young adults. Topical steroids remain the gold standard of treatment, but occasionally they fail to improve the condition, and the necessary prolonged use increases the risk of steroid-induced side effects. The aim of this research was to evaluate the efficacy and safety of a topical 0.005% tacrolimus eye drop for treatment of refractory VKC.Twenty eyes (10 subjects) diagnosed with refractory VKC that had failed to resolve with traditional treatment (everyone was given a 2-week steroid treatment of 0.1%
betamethasone eye drop with no improvement) were enrolled to undergo the tacrolimus treatment. Prior to and
throughout the treatment, patients were to fill out a questionnaire regarding symptoms of itching, redness, photosensitivity, foreign body sensation, and mucus discharge.The efficacy of the drop was determined by examination of signs and symptoms and by a patient’s need for additional therapeutic relief. Photos were taken at all visits and graded by 2 independent observers. There were no adverse effects or patient complaints regarding use of the tacrolimus drop.Overall, subjects seem to get rapid relief quickly from the treatment. By 1 month, most clinical signs and symptoms had been significantly reduced, and any attempts to discontinue the drop resulted in rapid recurrence of the condition. Topical 0.005% tacrolimus eye drops seem to be a safe and effective treatment for steroid-resistant refractory VKC, but continued use was necessary to maintain patient comfort. Cruzat A, Witkin D, Baniasadi N, et al. Inflammation and the Nervous System: The Connection in the Cornea in Patients with Infectious Keratitis. Invest Ophthalmol VisSci 52(8): 5136–5143, 2011.Corneal nerves play a vital role in corneal epithelial
integrity, proliferation, wound healing and protection. Additional protection is provided to the cornea by dendritic
cells, a type of antigen-presenting cell, which responds to invading pathogens. This study aims to evaluate the density and morphologic characteristics of epithelial dendritic-shaped cells (DC’s) and correlate them to any
decrease in corneal nerve density with infectious keratitis (IK). Previous work showed that in herpes simplex keratitis
cases with a reduction in corneal sensitivity, a simultaneous decrease in corneal nerves was found with in-vivo
confocal microscopy (IVCM). Fifty-three patients with a diagnosis of acute IK ( bacterial, fungal and Acanthamoeba) were included in the study. Twenty normal volunteers constituted the control group.IVCM (Heidelberg Retina Tomograph with Rostock Cornea Module) was performed on all subjects, with a resulting analysis and correlation of the following: density and morphology of dendritic-shaped cells (DCs) in the central cornea, corneal nerve density, number of dendrites per DC, nerve branching and nerve tortuosity. The IVCM revealed central corneal DCs in all patient groups. The mean DC density was significantly higher in patients with bacterial (441.1 cells/mm2), fungal (608.9cells/mm2), and Acanthamoebic keratitis (1000.2 cells/mm2) compared with controls (49.3 cells/mm2). DCs had an increased size in patients with acute IK. Corneal nervedensity (674.2 vs. 3913.9 μm/frame), corneal nerve
branches (1.2 vs. 13.5) and total number of nerves (2.7 vs.20.2) all showed a significant decrease in IK when compared to controls. Although nerve tortuosity was increased in IK, it was not statistically significant. A strong
association between decreased corneal nerves and an increase in DC density occurred (r = 0.44; P = 0.0005) in
patients with IK.
Dry Eye Disease
Meibomian gland expression is essential whenever a patient reports dry eye symptoms since obstructive meibomian gland dysfunction (MGD) may not always present with observable signs. Since MGD may be the leading cause of dry eye syndrome throughout the world,
removing gland obstruction is becoming increasingly important in the management of dry eye. Researchers investigated the pressure required (using a modified Mastrota paddle) to express the first non-liquid material from the meibomian gland. They also assessed the pressure required to empty the gland (the requirement for “therapeutic expression,” as defined by the authors) as well as the associated pain experienced by the patient.
It was determined that up to 40 psi could be required to satisfy the 2 outcome measures in gland expression.
Pain appeared to be the limiting factor to successful meibomian gland expression in most patients. A mean pressure of 16.1 psi was required for expression of the first non-liquid meibomian gland component, that was increased
to a mean pressure of 25.6 psi to evacuate the entire gland. As a comparison, the force generated by a forceful blink is around 0.3 psi. Despite the use of anesthetic drops, only 7% of study subjects could tolerate the pressure required for full therapeutic expression. The authors believe that although complete gland expression can be labor- and time-intensive (i.e., individual gland expression may take anywhere from 15 seconds to 2 minutes) and be associated with significant discomfort and lid swelling, it is an important and necessary tool in managing patients with MGD.Benzalkonium chloride (BAC) is a cationic surfactant often used as a preservative due to its inhibition of
bacterial growth during ophthalmic solution storage. Studies (in vivo) have indicated that BAC can decrease tear
film stability and create symptoms of dry eye. This study examined what the introduction of BAC does to the
surface properties of tear film components (meibum) and human tears overall. A collection of human meibum and whole tears was taken from 3 females (23–40 years old) and 1 male (31 years old); additionally, rabbit cornea cell cultures were investigated. Meibum samples were obtained by expressing the meibomian glands using 2 cotton-tipped applicators, with final harvesting of the meibum occurring through the use of a platinum spatula. In addition, a 25-microliter sample of tears was taken from each volunteer. The samples were examined using a variety of instrumentation to discover the effect of BAC on tear film and meibum (lipid) properties. Cell culture viability of a BACtreated Statens Seruminstitut rabbit cornea was also examined.The BAC concentration was kept within the clinical range of 0.001%–0.02%. Overall the study showed (1) an impaired lipid spread that caused non-uniform surface layers, (2) an increase in surface pressure-area hysteresis during compression and expansion, and (3) displacement of lipids by BAC from thesurface.It was also shown that these effects occurred within seconds of BAC exposure and increased in magnitude with BAC concentration. BAC also decreased the viability and confluence of cells in the rabbit culture model. These results are consistent with the clinical signs and symptoms of BAC use and may explain the disruption in tear film stability and corneal disruption that is observed. According to the Dry Eye Workshop, tear osmolarity has been highlighted as a key factor in determining the spectrum of dry eye severity. However, to date it remains unclear how this spectrum relates to clinical signs and symptoms. In relation to goblet cells, a reduced number of filled goblet cells, identified by PAS staining, has long been associated with dry eye disease and ocular surface inflammation.Other studies have hinted that this may create increased tear osmolarity. This study examined the effect of tear hyperosmolarity and signs of clinical ocular surface pathology on conjunctival goblet cell populations. Participants (n=111) had tear osmolarity assessed, as well as a comprehensive set of dry eye clinical tests performed. Tests included the following in this order: (1) biomicroscopic examination of the ocular surface, (2) lissamine green staining, (3) tear film break-up time using fluorescein, (4) fluorescein staining, (5) Schirmer strip evaluation, and (6) conjunctival impression cytology with PAS analysis. Tear film osmolarity was performed prior to the aforementioned tests using the TearLab Osmometer. Based on the tests performed during the study, the authors concluded that no statistically significant correlation existed between tear osmolarity and goblet cell number or function. However, there was a slight trend showing that with increasing osmolarity there was a decrease in the number of goblet cells. This trend was more obvious in subjects with severe goblet cell loss that would typify what is found clinically as a moderate dry eye patient. It might be suggested then that goblet cells have the ability to tolerate or adapt to a hyperosmolar environment.
Wu Y, Zhu H, Willcox, Stapleton F. The Effectiveness of Various Cleaning Regimens and Current Guidelines in Contact Lens Case Biofilm Removal. Invest Ophthalmol Vis Sci 52(1):5287–5292, 2011.
It is well known that bacterial adherence to contact lens cases can contribute to increased risk of microbial keratitis and ocular inflammation. This study evaluated the effectiveness of different case-cleaning regimens,case types (ridged vs. smooth) and multi-purpose disinfecting solutions (MPDS) in removing contact lens case
biofilm.Cases were “inoculated” with 2 different bacteria, Staph aureus and Pseudomonas aeruginosa. In addition, 2
different contact lens care systems were studied, Optifree Replenish (Alcon) and AMO COMPLETE EasyRub (AMO). Following manufacturer guidelines, Optifree Replenish appeared to remove a greater number of both Pseudomonas and Staph aureus. The combination of Optifree Replenish and the AMO contact lens case showed the greatest reduction in bacterial load. Although current manufacturers’ guidelines for casecleaning (i.e., “rinse and air dry”) reduce microbial adherence,researchers determined that these guidelines are not at all adequate in eliminating adherence altogether. The simple addition of rubbing the case with fresh MPDS for 5 seconds and tissue-wiping before allowing the case to air dry reduced bioloads up to 3–4 times compared to manufacturer recommendations in all solution and lens case types. It is no surprise to most that a “rub and rinse” cleaning
regimen (followed by a disinfection step), out-performs a “soak only,” and a “rinse only” regimen when it comes to
contact lens care with a multipurpose disinfection solution; however, such studies utilizing silicone hydrogel
lenses are scant. Researchers demonstrated that after allowing bacteria, fungi and acanthamoeba to adhere to a variety of lenses for 10 minutes (i.e., O2Optix, Acuvue Advance and Acuvue2), the “rub and rinse” method resulted in the lowest number of microbial survivors, regardless of lens type or solution used. Optifree Replenish seemed to outperform both Aquify and ReNu Multiplus solutions with regard to the “soak only” and “rinse only” regimens. Interestingly, data also suggests that Acuvue Advance lenses may bind bacteria less firmly than other lenses tested; there were fewer adhered bacteria after the “soak only” and “rinse only” regimens were performed. In the largest post-market observation regarding corneal inflammatory events (CIE) associated with soft contact lens (SCL) wear in children and teens, researchers concluded that use of SCLs in patients 8–15 years old was associated with a lower risk of infiltrative events compared with older teens and young adults.The peak age for SCL-associated CIEs seems to occur in persons between 15 and 25 years old. Authors hypothesize that the higher incidence of inflammatory events in this age group was multi-fold: the subjects in this group were typically college students living in on-campus housing without parental supervision and were inexperienced in seeking health care. College students anecdotally live a less healthy lifestyle, with poor nutrition and sleep habits and crowded living conditions. They may also have a decreased ability to purchase proper contact lens supplies and lens care products. Besides age, other major risk factors included extended wear and years of lens wear, which was in agreement with most previous reports. One new finding included the use of multipurpose solution, which tripled the risk of a CIE in this retrospective review. The authors hypothesize this may be because this study was conducted during the era
when no-rub solutions were at their peak.Contrary to previous thoughts, the signal for axiallength
growth appears to be driven by the peripheral retina, and may actually override visual input from an infocus
central fovea. Traditional myopic spectacles and contact lenses may inadvertently enhance this signal by
inducing peripheral retina hyperopic defocus. Recent short-term clinical trials targeting this hypothesis
are reviewed in this paper, which show great promise in treating this significant public health concern. Innovative
spectacles and contact lenses that decrease peripheral defocus (while maintaining central clarity), along with
overnight orthokeratology, executive bifocal spectacles and distance-center multifocal lenses, have all indicated
reduced myopia progression rates on the order of 36%–50% in certain age groups.The aim of this study was to evaluate and measure the effects on accommodative function for presbyopes and non-presbyopes wearing simultaneous image multifocal contact lenses (CLs). Six presbyopic patients were fitted with the Focus
Progressives and the low- and high-addition Pure Vision simultaneous vision multifocal CLs. All 3 lens types were
worn randomly, and the accommodative response, accommodative facility, visual acuity and contrast sensitivity at
distance and near were all measured. Mean age was 28.6±2.72 and 51.2±5.81 years in the non-presbyopes and
presbyopic patients respectively. For presbyopes, no statistically significant differences were found between distance visual acuity in all 3 lens types when compared to baseline visual acuity. The only significant difference was noted in near acuity, which improved using the high-add Purevision. The non-presbyopic subjects showed a relatively linear 1:1 stimulus response function across the board. Interestingly, this study showed that non-presbyopes
had no change in accommodation with the multifocal lenses, which conflicts with previous studies (though it
should be noted that different lens modalities were used in the current study).Overall, the take-home message is that simultaneousimage multifocal CLs studied do not statistically alter accommodative functions, and that a higher-add multifocal can aid advanced presbyopes with near acuity. Myopia progression treatment is a rapidly advancing
field of great interest to eyecare practitioners. Recent studies suggest that peripheral defocus may be a useful
tool in influencing overall refractive error. Based on this idea, a group from New Zealand proposed the Dual-focus Inhibition of Myopia Evaluation (DIMENZ) study to consider the advantages of Dual- Focus (DF) soft contact lenses as a possible treatment for myopia progression. In this randomized study, 40 children, 11–14 years old, with mean spherical equivalent refraction (SER) of -2.71±1.10 diopters (D) were prospectively followed. The lenses used were DF, with a central zone correcting the distance refractive error surrounded by peripheral concentric ring treatment zones, resulting in a 2.00D simultaneous myopic retinal defocus at both distance and near. Control was a single vision distance (SVD) lens with the same parameters but without treatment zones. The crossover study was broken up into 2 ten-month cycles where participants wore the DF lens in 1 randomly assigned eye for 10 months and the SVD in the fellow eye (period 1). After 10 months, the treatment was swapped and studied for another 10 months (period 2). Period 1 showed a change in the spherical equivalent refraction (SER) of -0.44 ± 0.33D versus the SVD lenses -0.69±0.38D (P=0.001). Mean increase in axial length (AXL) was less in the DF lens (0.11±0.09mm) when
compared to the SVD lenses (0.22±0.10mm) (P=0.001).Myopia progression was reduced by 30% in nearly ¾
of the children with the DF-wearing eye relative to the fellow eye wearing the SVD lens. Similar reductions and
differences were seen in period 2 when the lens modalities were switched. Visual acuity and contrast sensitivity with
the DF lenses were not significantly different than with SVD lenses.From the study it appears that DF lenses provided comfortable and adequate vision for the children. It also showed a clinically-significant decrease in SER and AXL for most subjects. Peripheral defocus may be an option in slowing the progression of myopia without decreasing visual acuity.
It is well known that the pressure to cornea index (PCI)
is a tool used to estimate the relative effects of the maximum
intraocular pressure (IOP) and central corneal thickness
(CCT in mm) to help categorize and aid in the diagnosis and treatment of glaucoma patients. This study proposes the use of an existing PCI in the prediction of field-progression in normal tension glaucoma (NTG) patients, and to determine if a modified index including vascular risk factors, pressure-cornea-vascular index
(PCVI), may be more useful. A cross-sectional analysis of a prospective cohort
study was conducted at Hong Kong Eye Hospital, a university-based tertiary eye center. Patients were recruited
between 2004 and 2005 and identified as NTG using 6 strict criteria. The study included 415 NTG subjects (184 fieldprogressed and 231 field-stable) analyzed over the course of 3 years. The PCI for these patients was calculated with a subsequent calculation of the PCVI. The vascular component was based on known biological factors as well as factors that appeared significant in a statistical analysis of visual field progression. These factors were then weighted by the investigators, and a series of combinations were analyzed. The definition of PCVI by the authors includes maximum IOP, age at presentation, vertical cup to disc ratio, hypertension,hemorrhage at the disc and corneal thickness. From these factors, a formula was derived to arrive at a PCVI index.Overall, the mean PCVIs were 113.1±76.8 and 69.7± 39.7 for field progression NTG and stable NTG groups,respectively (p<0.001). The authors concluded that PCVI may be especially useful for predicting progression in NTG by including the vascular component of hypertension.Further studies will be needed to validate the accuracy of PCVI in other NTG cohorts, such as different ethnicities. The reduction of intraocular pressures (IOP) has long been the goal of therapeutic treatment of glaucoma. Often the first line of defense is a monotherapy prostaglandin treatment.This study examines whether punctal occlusion of the superior and inferior plugs can increase the effects of a prostaglandin monotherapeutic treatment. Previous studies have shown that fingertip punctal occlusion may show a benefit, but to date no one has incorporated both superior and inferior punctual inclusion.Thirteen patients, over 18 years old, diagnosed with POAG or ocular hypertension from the Illinois Eye Institute,were recruited for this prospective study. The patients were on travaprost 0.004%, with stable IOP for a minimum of 1 year and no progression of visual field defects or nerve-head damage. Each patient also had to report compliance with the treatment for a minimum of 3 months.Baseline IOPs were measured and silicone plugs (Oasis plugs) were placed into the superior and inferior puncta of one eye; the fellow eye served as the control. The patient was instructed to continue using travaprost as before and to return in 1 month for an IOP check. Eleven of the 13 patients completed the study. One
subject dropped out due to excessive tearing, and 5 of the remaining 11 had a similar complaint. The 1-month visit
yielded a relative decrease in IOP of 1.59 mmHg or a 6.82% decrease as compared to a 1.91% increase in the
control eye (p=0.01). Punctal occlusion of both puncta seems a safe and effective adjunct to obtain a desired
decrease in IOP if trying to keep the patient on monotherapy.