Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
AMO Resident Most Challenging Contact Lens Case Catherine Pannebaker, O.D. INTRODUCTION Keratoconus is an asymmetric condition of corneal ectasia and thinning with onset usually in early teens to early twenties, with an incidence of about 1/2000 [1]. Patients can be markedly visually impaired with high amounts of irregular astigmatism and myopia. Classic objective signs seen by biomicroscopy include stromal thinning, central scarring, vertical lines in the posterior cornea (Vogt’s striae), and prominent corneal nerves; quite often a brownish or olive green colored ring of iron deposition (Fleischer’s ring) is seen at the base of the “cone” or apex of the protrusion. Additional signs include a bowing outward of the inferior lid in downgaze (Munson’s sign) and steepened keratometry or topography readings. In some advanced cases of keratoconus, breaks in the posterior cornea can occur. This causes an influx of aqueous humor, and leads to an acute and painful onset of corneal edema. These episodes of corneal hydrops usually result in scarring. Fibrotic scarring near the visual axis and apex of cone are also evident in many patients even in the absence of hydrops. Although improved with pinhole, the best corrected visual acuity in keratoconus patients is often reduced with spectacle correction; therefore, most patients are managed with rigid gas permeable contact lenses in a wide range of specifications. Some patients may require penetrating keratoplasty if contact lenses are no longer a management option. Keratoconus is historically defined as a non-inflammatory condition. The exact etiology is unknown, however, recent literature suggests that inflammation molecules 1 AMO Resident Most Challenging Contact Lens Case Catherine Pannebaker, O.D. and abnormal levels of enzymes are present in patients with keratoconus [2,3]. Other research indicates that keratoconus may also have genetic components [4]. Frequent associations include history of allergies, atopy (asthma, hay fever, eczema), eye rubbing, eye injuries, rigid contact lens wear, and family history of keratoconus [5]. Curiously, the condition seems to cease progression with increasing age [6,7]. The sections to follow will summarize literature regarding studies on related proteins in corneal tissues and tears, as well as possible genetic and inflammatory aspects involved in the etiology and progression of keratoconus. Tear Proteins Extensive tear protein work performed by Souza et al has resulted in the identification of 491 proteins, both extracellular and intracellular, the latter of which may result from cell death in the epithelium of the cornea [8]. Many proteins are contained in the aqueous layer of the tears and are secreted by the lacrimal and accessory glands. The majority of these proteins in the normal tear film consist of lysozyme, lactoferrin, secretory immunoglobulin A, serum albumin, lipocalin, and lipophilin [9]. In addition, these proteins are in a relatively high concentration (8 ųg/ųL), and easily accessed in tear collection methods, making the tear film very promising for extensive protein analysis via such methods as enzyme-linked immunosorbent assay (ELISA), mass spectrometry and others [8]. The study of proteins, or proteomics, is valuable in identification of molecular markers involved in such processes as wound healing, the immune response, inflammation, and oxidative stress, or damage to tissues resulting from the inability to process reactive oxygen species. 2 AMO Resident Most Challenging Contact Lens Case Catherine Pannebaker, O.D. Tissue and Ocular Surface Disorder Teng used electron microscopy in the 1960’s to investigate the pathologic changes in the corneal tissue of keratoconus patients [10]. He confirmed the decomposition of the basement and Bowman’s membranes, and stated that the result of enzyme activities could affect collagen and nerve fibers along with Descemet’s membrane. Additional studies by Jongebloed and Sawaguchi revealed not only a lack of replacement of epithelial cells leading to holes exposing Bowman’s membrane in some areas, but also an “accelerated aging process” in the epithelium [11-14]. Murat Dogru et al studied changes in the ocular surface in terms of corneal staining, goblet cell density, and squamous metaplasia using standard Schirmer testing and impression cytology; these tests were performed on mild to severe keratoconus patients who had no history of contact lens wear, ocular surgery or other active systemic or eye conditions [14]. They found that nearly 46.6% of the eyes had punctate keratopathy and 70.6% had a tear breakup time <10 seconds; squamous metaplasia was an average of 10 times greater in the keratoconus eyes verses control eyes, and goblet cell density was half that of control eyes [14]. The significance of the squamous metaplasia is that an actual transformation of tissue has occurred. Goblet cells are important in producing mucins: glycoprotein secretions known to create a hydrophilic ocular surface and therefore aid in tear film stability [15-16]. An interesting finding in Dogru’s study was that Schirmer testing revealed no significant differences between the keratoconus eyes and control eyes, suggesting an absence of aqueous-deficient dry eyes [14]. Dogru 3 AMO Resident Most Challenging Contact Lens Case Catherine Pannebaker, O.D. suggested the possibility of new approaches in therapies for keratoconus patients. These therapies include topical retinoids, which have been shown to aid in producing basement membrane components, and topical 15-(S)-hydroxyeicosatetraenoic acid for increasing mucin secretions [12]. This study and others to be discussed may be suggestive of tissue and tear function abnormalities in keratoconus. Genetic Studies Numerous genetic studies have been performed with the hope of discovering a gene that is solely responsible for keratoconus. Noting that keratoconus has systemic and familial associations, genetics most likely plays a role in the etiology [17]. Furthermore, the variability displayed in families, the asymmetry with which the eyes are affected, and discordance between mono- and dizygotic twins supports a genetic component [18-20]. There are a few cases of monozygotic twins in which one had clinical signs of keratoconus, and the other lacked any signs – even with topography – owing evidence that environmental aspects play a role as well [19]. Both dominant and recessive inheritance patterns have been seen in families, and the variable expression of keratoconus remains puzzling [21-23]. However, the development of corneal topography now enables a method of early detection in the condition, which further helps to clarify pedigrees and prevalence in families as it is used to test family members and show similarities in the cone presentation (e.g., central, inferior) [24,25]. Keratoconus has proven associations with Down syndrome (10-300 fold increase in prevalence), Leber’s congenital amaurosis, atopy and connective tissue disorders; these associations can be important in providing chromosomal information since these 4 AMO Resident Most Challenging Contact Lens Case Catherine Pannebaker, O.D. disorders have a defined genetic origin [26]. The most compelling systemic association is with mitral valve prolapse, as Beardsley and Sharif found 44% and 58% prevalence in their subjects respectively, possibly indicating a link with collagen abnormality [26-28]. Unfortunately, some genetic studies in the past used inconsistent methods, and many were conducted mostly on caucasians [29-30]. Rabinowitz recently recruited hispanic, black, and asian subjects in addition to whites and found some consistency in linkage between whites and hispanics [17]. He found evidence of linkage to keratoconus on chromosomes 4, 5, 9, 12, and 14 for whites “and/or all pedigrees”, and additionally chromosome 17 for Hispanics only [17]. Specifically, Rabinowitz targeted three candidate keratoconus genes from these chromosomes: lysyl oxidase, a gene responsible for collagen cross-linking; cell death-inducing DEFA-like effector b, thought to be involved in apoptosis; and gelsolin, a gene also associated with another corneal dystrophy [17]. Although his study could only conclude that many loci are involved in keratoconus, it was the first of its kind with a large sample size (351 subjects phenotyped) to identify linkage in populations other than whites, and will most likely challenge other scientists to recruit a variety of subpopulations [17]. In addition, Rabinowitz has shown linkage to other chromosomes – 3, 13, 15, 16, 17, 20, and 21 (significant in trisomy 21), yet the exact genetic cause for keratoconus is still not clear in that genes were not found at the precise loci [31,32]. Although associated with polymorphous corneal dystrophy, the visual system homeobox 1 gene (VISX1) has been widely speculated as a possible mutation involved in keratoconus [33-35]. Aldave et al recently disproved this in a study of four specific 5 AMO Resident Most Challenging Contact Lens Case Catherine Pannebaker, O.D. mutations, showing that VSX1 gene mutations are not associated with the etiology of keratoconus [35]. Udar et al recently studied superoxide dismutase 1 (SOD1) along with Christina Kenney’s group as a possible candidate gene in keratoconus [32]. Superoxide dismutase on chromosome 21 is an enzyme known to be involved in antioxidant activities by reducing accumulating free radicals [32]. Although mutations in the gene were found, the evidence was not conclusive, and no causal relationship between these mutations of SOD1 and keratoconus could be confirmed; further studies were suggested with other variants of the gene [32]. Inflammation and Immune Response Although keratoconus is defined throughout the literature and textbooks as a noninflammatory condition, several studies support the possibility of inflammatory and immune molecules at work in this condition. Atopy, a genetically determined state in which the body elicits an exaggerated response to a foreign stimulus, is known to be associated with increased levels of immunoglobulin E (IgE) [15,36]. In 1982, Kemp and Lewis reported elevated serum levels of IgE in 59% of 27 keratoconus patients selected at random [37]. Rahi et al reported increased serum levels of IgG and IgM in keratoconus patients, while Kemp and Lewis found no statistically significant difference in these immunoglobulins in keratoconus patients compared to controls in their study [37,38]. Although an association between eye rubbing in patients with allergic conditions has been widely reported by several studies, many clinicians and researchers view it as a 6 AMO Resident Most Challenging Contact Lens Case Catherine Pannebaker, O.D. difficult correlation to make due to the nature of self-reported episodes. It is feasible, however, that these patients rub may their eyes as a result of an already present allergic reaction taking place. In 2005, Lema and Durán studied one eye each from 28 patients diagnosed with keratoconus [36]. They targeted specific cytokines, cell adhesion molecules, and matrix metalloproteinase 9 (MMP-9). Cytokines, cell adhesion molecules and MMP-9 were chosen for their association with chronic inflammation [36]. Tear samples of 15 ųLs were collected from keratoconus subjects who had not worn contact lenses, and had no active inflammatory systemic or ocular conditions, and then processed with ELISA kits. Three molecules were found to be at levels significantly higher than normal in keratoconus patients: IL-6, TNF-α, and MMP-9. In addition, the levels of each molecule were strongly correlated with the severity of keratoconus. Following regression analysis, however, only MMP-9 was found to be an independent variable associated with the degree of keratoconus. Lema made a compelling remark: “It can be concluded…that keratoconus cannot be defined any more as a noninflammatory disorder” [36]. In his review article from 2001, Simon Collier addresses MMPs and their possible role in keratoconus [39]. He specifically addresses the absence of upregulation of MMP9 by Fini, Kenny, and Zhou by suggesting that techniques could be a possible source of conflict [39-42]. Collier additionally notes that MMP-9 should be induced by IL-1, and Fabre et al noted that keratoconus fibroblasts release fourfold the number of these same IL-1 receptors compared to normal corneas [39,43]. It would stand to reason therefore, that MMP-9 could indeed be overexpressed in keratoconus. 7 Furthermore, Li and AMO Resident Most Challenging Contact Lens Case Catherine Pannebaker, O.D. Pflugfelder report that MMP-9 may be “a most amplifying factor for corneal inflammation” [44]. Other researchers have seen expression of similar molecules in keratoconus patients. Collier et al were first in demonstrating the expression of membrane-type 1 (MT1) MMP in vivo in keratoconus corneas compared to controls [45]. Ohuchi and D’Ortho had found previously that MT1-MMP can activate gelatinase A to digest type IV collagen of the basement membrane; MT1-MMP has the ability to degrade several extracellular matrix molecules including collagen types I-III [46,47]. It is important to note that the cornea is 70% collagen by weight and is mostly comprised of Type I collagen [39]. The ectasia and thinning found in keratoconus is mostly due to a damaged extracellular matrix and a decrease in types I and IV, along with an increase in type IX collagen – not otherwise found in the basement membrane of the cornea. [39,48]. Collier et al further hypothesized that MT1-MMP could be released in response to an inflammatory-related or pathological event, and that it most likely has a significant role in the etiology if not the progression of keratoconus [45]. Abalain et al studied levels of telopeptides, or collagen degradation products from 26 keratoconus subjects and 36 controls [48]. This study allowed contact lens wear and an average of 2-7 ųL was collected; active inflammation, ocular surgery and topical ocular medications were exclusions [48]. The concentration of telopeptides was found by ELISA kits, and keratoconus patients were found to have 3.5 times the amount of telopeptides compared to normals; contact lens wear did not significantly modify the amounts [48]. It was hypothesized that corneal thinning may result from proteolysis of collagen rather than a decrease in the synthesis of extracellular components [48]. 8 AMO Resident Most Challenging Contact Lens Case Catherine Pannebaker, O.D. Degradative Enzymes/Oxidative Processes In a hallmark review paper, Christina Kenney and Donald Brown describe a “cascade hypothesis of keratoconus” in which enzymes in two pathways could lead to oxidative damage [49]. She notes a decrease in the inhibitors of destructive enzymes are decreased in keratoconus corneas; they are alpha one (α1) proteinase inhibitor, alpha two (α2) macroglobulin, and tissue inhibitor metalloproteinase one (TIMP-1); the latter of which can inhibit cell apoptosis (programmed cell death) and affect cell growth [15,42,49,51]. Matthews et al noted that relative concentrations between TIMP-1 and TIMP-3 could be determinants in the balance of cell overgrowth and apoptosis in keratoconus [52]. Importantly, apoptosis occurs in normal cellular turnover as well as diseases and wound healing [49]. Edwards et al hypothesized that apoptosis could also occur from the release of inflammatory cytokines from injured corneal and conjunctival epithelial cells [26]. Gondhowiardjo et al noted a decrease in aldehyde dehydrogenase Class 3 (ALDH3) and superoxide dismutase, the necessary enzymes to process reactive oxygen species (ROS), and Kenney surmises that this leads to large amount of cytotoxic by products in keratoconus corneas eventually leading to corneal thinning and loss of vision [49,53,54]. Kenney recommends that clinicians educate patients on sources of reactive oxygen species such as ultraviolet (UV) light, trauma caused by excessive eye rubbing and poorly fit contact lenses, and uncontrolled allergies. In addition she recommends UV 9 AMO Resident Most Challenging Contact Lens Case Catherine Pannebaker, O.D. protection in both contact lenses and glasses, and prescribing of topical non-steroidal anti-inflammatory medications (NSAIDS) and allergy medications, as well as preservative-free artificial tears in the management of keratoconus patients [49]. CASE REPORT Pertinent History and Chief Complaint Patient AC, a 26-year-old white female, was referred to the clinic by a local practitioner for contact lens fitting in March, 2007. She had been fitted with soft toric contact lenses in December of 2006, and was reporting fluctuating and decreased vision with both her contact lenses and spectacles over the previous two years. AC’s occupation was programmer, and her systemic history was unremarkable; she reported taking oral birth control medication. Other pertinent patient and family history was unremarkable. The patient’s comprehensive examination in December, 2006, revealed that pupils, motilities, and color vision were within normal limits in both eyes, although local stereopsis was reduced at 50”. Vision with her current spectacles was 20/30 OD and 20/40 OS. The manifest refraction determined was -2.75 -4.75 x 057 (20/30) in the right eye, and -3.75 -4.50 x 132 (20/30) in the left eye. The soft toric contact lens prescription had not been finalized, but trials of Vertex Toric had been dispensed: Median base curves, 14.4mm diameter and powers of -3.00-2.75 x045 in the right eye, and -3.50 -3.75 x155 in the left eye. The previous practitioner had noted no abnormalies with biomicroscopy, and non-contact tonometry revealed introcular pressures of 6 mmHg in both eyes at 5pm. Confrontations and amsler grid testing were reported within normal limits in both eyes. Dilation with 1% Tropicamide revealed that all aspects of the posterior pole and peripheral fundus examination were within normal 10 AMO Resident Most Challenging Contact Lens Case Catherine Pannebaker, O.D. limits in each eye. Their impression was myopic astigmatism and slightly reduced acuities in each eye, and plan was to refer to OSU clinic for further contact lens fitting. Contact Lens Fitting – First Visit (4/06/07) Entrance Distance Visual Acuity (Snellen, with CL’s) OD: 20/25 OS: 20/50 (PH 20/30) Pupils: 5/5 Round/reactive to light with no afferent pupillary defect OU Current Soft Contact Lens Assessment OD Minimal Slightly inf Adequate 9º Nasal Movement Centration Coverage Rotation OS Minimal Slightly Inf Adequate 10º Nasal Manifest Refraction (D) OD: -2.75 -4.50 x048 20/25 OS: -4.00 -4.50 x132 20/30 PHNI Simulated Keratometry Readings (Medmont – see pp. 11-12) OD: 48.8 D @ 134 / 42.7 D @ 044 Trace distortion of mires OS: 49.4D @ 048 / 42.10D @138 Trace distortion of mires Biomicroscopy: OD Make-up debris Trace injection See drawing Blue/clear Von Herrick G4 Lids/Lashes Conjunctiva Cornea Iris Anterior Chamber OS Make-up debris Trace injection See drawing Blue/clear Von Herrick G4 .75mm vascularization OD/OS Corneas: 1+ SPK (-) Fleisher’s Ring OD/OS 1+ SPK inf OD OS Stromal thinning seen with slit lamp beam 11 AMO Resident Most Challenging Contact Lens Case 12 Catherine Pannebaker, O.D. AMO Resident Most Challenging Contact Lens Case 13 Catherine Pannebaker, O.D. AMO Resident Most Challenging Contact Lens Case Catherine Pannebaker, O.D. Contact Lens Fitting OD (9.5mm diameter PMMA fitting set, with 8.1mm Optic Zone (OZ) and 8.40/10.5 secondary and peripheral curves) 1 drop Proparacaine instilled OD prior to fitting 1) BC = 7.3/-3.00 (Approximately Average of K readings) Fit Central Flourescein Pattern Edge Lift Other Lid Attached (LA) Central Pooling Minimal 360º Mid peripheral bearing 2) BC = 7.5/-3.00 (Slightly flatter since central pooling) Fit Central Flourescein Pattern Edge Lift Other LA Feather touch Minimal 360º Slight Mid peripheral bearing Spherical over-refraction (SOR) -5.00D (vertexed power -4.75, 20/20) Contact Lens Fitting OS (9.5mm diameter PMMA fitting set, with 8.1mm OZ and 8.40/10.5 secondary and peripheral curves) 1 drop Proparacaine instilled OD prior to fitting 1) BC = 7.2/ -3.00 (Approximately Average of K readings) Fit Central Flourescein Pattern Edge Lift Other LA Central pooling Minimal 360º Central Bubble 2) BC = 7.5/-3.00 (Since central pooling/bubble) Fit Central Flourescein Pattern Edge Lift Other LA Slight pooling Minimal 360º Small Central bubble 3) BC = 7.6/-3.00 (Since still central pooling/bubble) Fit Central Flourescein Pattern Edge Lift Other Interpalpebral – inf centration Trace pooling @ feather touch Minimal 360º No bubbles SOR -5.75D (vertexed power -5.37, 20/20) 14 AMO Resident Most Challenging Contact Lens Case Catherine Pannebaker, O.D. Final Contact Lens Order – based on spherical over-refractions and flourescein patterns and trial lens parameters Base Curve (BC) OD OS 7.5 7.5 Optic Zone Diameter (OZD) 7.7 7.6 Secondary Curve Radius/width in mm (SC/width) 8.4 / .7 8.4 / .75 Peripheral Curve Radius/width in mm (PC/width) 10.5 /.2 10.5 /.2 Overall Power Diameter (OAD) 9.5 9.5 -7.75 -8.37 Materials: Fluoroperm (FP) 60; Blue Tint (dot OD) Assessment Plan 1) Mild Keratoconus OD/OS 1) Ordered gas permeable lenses above. Flatten peripheral curves to increase - improvement in vision OD/OS with edge clearance in both eyes. gas permeable contact lenses today FP 60 material ordered - Medmont Topography performed for increased oxygen permeability given power. Application/removal instruction - Discussed benefits of GP vs soft toric at dispense. Gave patient sample of lenses. artificial tears (ATS) twice or more daily each eye. Educated pt about nature of condition and possibility of several visits ahead. First Dispense Visit (4/20/07) Pertinent new history: Patient using artificial tears 2-4 times daily; No changes in systemic health since last visit. Entrance Distance Visual Acuity (Snellen, with SCL’s) OD: 20/25 OS: 20/50 (PH 20/30) Dispensed new contact lenses in previously ordered parameters and allowed to settle 20 minutes Visual Acuity with new contact lenses OD: 20/20 OS: 20/20 Contact Lens Evaluation OD OS LA(falls after few seconds) LA (falls after few seconds) Fit Central Flourescein Feather touch w/ slight pool Feather touch w/ slight pool inf/sup inf/sup Pattern Adequate except minimal @ 3/9 Adequate except minimal @ 3/9 Edge Lift No over-refraction performed this visit since 20/20 vision 15 AMO Resident Most Challenging Contact Lens Case Catherine Pannebaker, O.D. Patient completed application and removal process along with cleaning regimen Diagnostic Assessment and Plan Adequate fit today OD/OS with rigid contact lenses. Application and removal process successful. Gave patient Boston Simplus Solution. Pt to wear CL’s 3 hours today plus 1 hour daily until 1 week check. Continue artificial tears 2-4 times daily OD/OS. Pt understands to call clinic immediately if pain redness or decrease in vision occurs. One week check (04/27/07) Pertinent new history: Unremarkable Entrance Distance Visual Acuity (with new GP lenses) OD: 20/20 OS: 20/20 Over-refraction OD: Plano OS: Plano Contact Lens and surface evaluation OD Poor LA/falls immediately Fit Central Flourescein Pattern Feather touch w/ slight pool inf/sup Poor 360º Edge Lift Good wettability; no Other deposits Biomicroscopy without CL’s: OD Makeup debris Trace injection G1 3/9 stain Lids/Lashes Conjunctiva Cornea/staining OS Poor LA/falls immediately Feather touch w/ slight pool inf/sup Poor 360º Good wettability; no deposits OS Makeup debris Trace injection G1 3/9 stain Continue with CL fitting since poor fit OD/OS Contact Lens Fitting OD (10.8mm diameter Dyna Z Intral Limbal, with 9.0mm OZD) 1) BC = 7.85/-1.37 (Approximately flat K readings) Fit Central Flourescein Pattern Edge Lift Other Lid Attached (LA) Central Pooling Adequate except lift off inferior Good centration and movement SOR OD -4.00 (vertexed power -3.87) 16 AMO Resident Most Challenging Contact Lens Case Catherine Pannebaker, O.D. Contact Lens Fitting OS (10.8mm diameter Dyna Z Intral Limbal, with 9.0mm OZD) 1) BC = 7.85/ -1.37 (Approximately Average of K readings) Fit Central Flourescein Pattern Edge Lift Other LA Slight central touch Lift off inferior Nasal centration 2) BC = 7.67/-1.75 (Since central touch and inferior lift off) LA Fit Feather touch Central Flourescein Pattern Good except inf lift off Edge Lift Better centration Other SOR -4.25 (Vertexed power -4.00, 20/20) Final Contact Lens Order – based on spherical over-refractions and flourescein patterns and trial lens parameters BC OZD OD 7.85 9.0 OS 7.67 9.0 Peripheral Curve OAD Parameters 1 step flat with 3 steps 10.8 flat @ 270º 1.0 Prism 1 step flat with 3 steps 10.8 flat @ 270º 1.0 Prism Power -5.25 -5.75 Material – Menicon Z Diagnostic Assessment and Plan Inadequate fit with previously dispensed GP CL’s. Refit today with Dyna Z IL CL’s in above parameters. Pt to return to SCL wear until new CL’s arrive. Continue ATs at least two times daily. Dispense Visit (5/11/07) Pertinent new history: Patient using artificial tears 2-4 times daily; No changes in systemic health since last visit. Entrance Distance Visual Acuity (with SCL’s) OD: 20/25 OS: 20/50 (PH 20/30) Dispensed new contact lenses in previously ordered parameters and allowed to settle 20 minutes Visual Acuity with new contact lenses OD: 20/20 OS: 20/20 17 AMO Resident Most Challenging Contact Lens Case Catherine Pannebaker, O.D. Contact Lens Evaluation OD LA (falls after few seconds) Fit Central Flourescein Feather touch w/ slight pool inf/sup Pattern Slightly excessive inferiorly Edge Lift OS LA (falls after few seconds) Feather touch w/ slight pool inf/sup Slightly excessive inferiorly No over-refraction performed this visit since 20/20 vision Diagnostic Assessment and Plan Adequate fit with Dyna Z IL CL’s for Keratoconus OD/OS. Instructed pt to build up wearing time again, and to only use Boston Simplus solution for cleaning. RTC one week for check. One week check (05/18/07) Pertinent new history: Pt reports slight dryness with CL’s after 8 hours; using ATs 4x daily. Entrance Distance Visual Acuity (with new GP lenses) OD: 20/20 OS: 20/20 Over-refraction OD: Plano OS: Plano Contact Lens and surface evaluation OD Poor LA/falls immediately Fit Central Flourescein Pattern Feather touch w/ slight pool inf/sup Adequate; increased inf Edge Lift Poor wettability; a few Other deposits present OS Poor LA/falls immediately Feather touch w/ slight pool inf/sup Adequate; increased inf Poor wettability; a few deposits present Biomicroscopy without CL’s: Lids/Lashes Conjunctiva Cornea/staining OD Makeup debris G1 nasal injection G1 3/9 stain OS Makeup debris G1 nasal injection G1 3/9 stain Cleaned lenses with Boston Lab cleaner in office today to remove deposits 18 AMO Resident Most Challenging Contact Lens Case Catherine Pannebaker, O.D. Diagnostic Assessment and Plan Adequate fit with Dyna Z IL CL’s for Keratoconus OD/OS, yet dryness symptoms with decreased wettability and surfacde deposits present this visit. Some staining and injections present this visit. Cleaned lenses in office today. Pt to limit wear time to 8 hours until next visit and continue ATs 2-4x daily. Consider refit next visit if necessary. Instructed pt to build up wearing time again, and to only use Boston Simplus solution for cleaning. RTC one week for check. Contact Lens check (05/30/07) Pertinent new history: Eyes feel dry after one hour. Yesterday night OS CL dislodged causing slight redness, tearing and pain. Using ATs liberally since last night Entrance Distance Visual Acuity (with new GP lenses) OD: 20/20 OS: 20/20 Over-refraction OD: Plano OS: Plano Contact Lens and surface evaluation OD Poor LA/falls immediately Fit Central Flourescein Pattern Feather touch w/ slight pool inf/sup Adequate except slightly Edge Lift increased inf Poor wettability; a few Other deposits present Biomicroscopy without CL’s: Poor wettability; deposits present a few OS Makeup debris G1 nasal injection Paracentral corneal abrasion 2.5mm in length which picks up stain Diagnostic Assessment and Plan Paracentral corneal abrasion OS d/t dislodged CL. Pt to discontinue CL wear and wear spectacles. Prescribed Vigamox ophthalmic solution 1gt q1hr OS while awake. Pt to return tomorrow for cornea check. Advised decrease in makeup to avoid infection. Gave cell number and told pt to call if any changes such as discharge develop. Lids/Lashes Conjunctiva Cornea/staining OS Poor LA/falls immediately Feather touch w/ slight pool inf/sup Adequate OD Makeup debris Slight injection G1 3/9 stain OS Cornea check (05/31/07) Pertinent new history: Pt using Vigamox 1gt q1hr OS, and reports no discharge, redness or pain this visit. 19 AMO Resident Most Challenging Contact Lens Case Entrance Distance Visual Acuity (with spectacles) OD: 20/30 OS: 20/40 Biomicroscopy: Lids/Lashes Conjunctiva Cornea/staining Catherine Pannebaker, O.D. OD Trace Makeup debris trace injection Trace SPK 3/9 OS Trace Makeup debris trace injection G1 Stain over 1mm abrasion Diagnostic Assessment and Plan Paracentral corneal abrasion OS d/t dislodged CL much improved. Pt to continue CL wear Vigamox qid OS and one week for cornea check and possible refit of CL’s. Pt to wear spectacles until that time. Re-educated pt about nature of condition and will try yet a different type of lens on next visit to get a good fit. Pt enjoys the vision of GP lenses and willing to be refit for corneal health. OS Cornea check and possible CL fit (06/08/07) Pertinent new history: Pt using Vigamox 1gt qid OS, and reports no discharge, redness or pain this visit. Entrance Distance Visual Acuity (with spectacles) OD: 20/30 OS: 20/40 Biomicroscopy: Lids/Lashes Conjunctiva Cornea/staining OD Trace Makeup debris trace injection clear OS Trace Makeup debris trace injection Clear – no abrasion present Contact Lens Fitting OD (11.2mm diameter Rose K IC) 1) BC = 7.85/-5.00 (same as previously fit GPs) Definite Central Touch Central Flourescein Pattern 2) BC = 7.67/-5.00 (since central touch) Central Flourescein Pattern Central Touch 3) BC 7.34/-5.00 (since central touch) 20 AMO Resident Most Challenging Contact Lens Case Contact Lens Evaluation Fit Central Flourescein Pattern Edge Lift Catherine Pannebaker, O.D. OD LA Alignment pattern Minimal at 3/9 SOR OD -3.00 (20/20) Contact Lens Fitting OS (11.2mm diameter Rose K IC) 1) BC = 7.67/-5.00 (same as previously fit GPs) Some Central Touch Central Flourescein Pattern 2) BC = 7.50/-4.00 (since central touch) Contact Lens Evaluation Fit Central Flourescein Pattern Edge Lift Other BC OD OS OD LA Alignment pattern Minimal at 3/9 Few midperipheral bubbles SOR OD -3.50 (20/20) Contact Lens Order – based on spherical over-refractions and flourescein patterns and trial lens parameters; consulted with lab about minimal edge lift at 3/9 OD/OS. Toric peripheral curves recommended. OZD 7.34 Proprietary 7.50 Proprietary Material Boston EO Peripheral Parameters Step 1 Toricity Step 1 Toricity Curve OAD Power 11.2 11.2 -8.00 -7.50 Diagnostic Assessment and Plan Paracentral corneal abrasion OS resolved. Pt refit this visit into Rose K IC reverse geometry design OD/OS. Pt to discontinue Vigamox OS and use ATs 2-4x daily and wear spectacles until dispense visit. Dispense Visit (6/22/07) Pertinent new history: Patient using artificial tears 2-4 times daily; No changes in systemic health since last visit. 21 AMO Resident Most Challenging Contact Lens Case Catherine Pannebaker, O.D. Entrance Distance Visual Acuity (with spectacles) OD: 20/30 OS: 20/40 Biomicroscopy: OD OS Trace Makeup debris Trace Makeup debris Lids/Lashes trace injection trace injection Conjunctiva clear Clear – no abrasion present Cornea/staining Dispensed new contact lenses in previously ordered parameters and allowed to settle 20 minutes Visual Acuity with new contact lenses OD: 20/20 OS: 20/20 Contact Lens Evaluation OD OS Central alignment Central Flourescein Central alignment Pattern Minimal 360º Minimal 360º Edge Lift Minimal movement Minimal movement Other The contact lenses were modifed in office at this point to attempt to dispense at this visit. A 12.50mm tape tool was used to modify the peripheral curves of each contact lens with the goal of increasing edge lift and movement for adequate tear exchange. This modification process was performed in small increments a total of three times. The lenses were cleaned with Boston lab cleaner following modification. Visual Acuity with modified lenses OD: 20/20 OS: 20/20 Contact Lens Evaluation after modification OD OS Central alignment Central Flourescein Central alignment Pattern Good 360º Good 360º Edge Lift Good movement Good movement Other Diagnostic Assessment and Plan Adequate fit achieved today with Rose K IC CL’s OD/OS following inoffice modification. Pt to slowly increase wearing time and RTC within two weeks for progress check. Contact Lens check (07/02/07) Pertinent new history: Pt reports good vision and comfort with modified Rose K IC CL’s OD/OS. Pt using ATs prn. 22 AMO Resident Most Challenging Contact Lens Case Entrance Distance Visual Acuity (with new GP lenses) OD: 20/20 OS: 20/20 Over-refraction OD: Plano OS: Plano Contact Lens and surface evaluation OD Central Flourescein Central alignment Pattern Good 360º Edge Lift Good movement; no deposits Other Catherine Pannebaker, O.D. OS Central alignment Good 360º Good movement; no deposits Biomicroscopy without CL’s: OD OS Trace makeup debris Trace makeup debris Lids/Lashes Trace injection Trace injection Conjunctiva Trace 3/9 stain Trace 3/9 stain Cornea/staining Diagnostic Assessment and Plan Good fit, vision and comfort with modified Rose K IC GPs for keratoconus OD/OS. Pt to return in one month for progress check. RTC sooner if problems arise. Contact Lens check (08/03/07) Pertinent new history: Unremarkable Entrance Distance Visual Acuity (with GP lenses) OD: 20/20 OS: 20/20 Over-refraction OD: Plano OS: Plano Contact Lens and surface evaluation OD Central Flourescein Central alignment Pattern Good 360º Edge Lift Good movement; trace deposits Other OS Central alignment Good 360º Good movement; trace deposits Contact lenses cleaned with Boston lab cleaner in office today. Pt educated on Lobob Optimum system for cleaning contact lenses more thoroughly. 23 AMO Resident Most Challenging Contact Lens Case Catherine Pannebaker, O.D. Biomicroscopy without CL’s: OD OS Trace makeup debris Trace makeup debris Lids/Lashes Trace injection Trace injection Conjunctiva Trace 3/9 stain Trace 3/9 stain Cornea/staining Diagnostic Assessment and Plan Good fit, vision and comfort with modified Rose K IC GPs for keratoconus OD/OS. Trace deposits on lenses today. Contact lenses cleaned and pt educated about Lobob Optimum cleaning system for thorough cleaning of lenses. Pt to return to clinic if necessary if problems arise before comprehensive examination in March. Pt pleased. DISCUSSION Keratoconus can be managed using many contact lens types to provide good vision and comfort for the patient. Smaller and steeper designs of gas permeable lenses are usually used for smaller, more centrally located “cones” or focalized areas of corneal ectasia. As the area of the cone increases and/or appears more inferior, larger diameter lenses with larger optic zones tend to be used. In the case of AC, initial topography readings showed a medium-sized area of slightly inferior ectasia, therefore, large diameter lenses were fitted. The smaller topography platforms are recommended for their increased number of areas of calculation for irregular corneas, and therefore the Medmont platform was utilized for an increase in accuracy of the simulated keratometry readings [55]. Another interesting point about topography is that, although keratoconus corneas usually present with irregular astigmatism, the mathematical algorithm built into most platforms is designed to give simulated keratometry readings showing regular astigmatism [55]. This is a very minor issue given the fact that topography has revolutionized the ability to diagnose keratoconus and other corneal abnormalities over the past few decades. Patient 24 AMO Resident Most Challenging Contact Lens Case Catherine Pannebaker, O.D. AC’s maps revealed the possibility of an emerging “kissing bird” appearance often associated with Pellucid Marginal Degeneration (PMD); this was yet another reason to concentrate on larger lenses at the fittings, as most clinicians agree that a larger diameter lens has improved success with PMD patients. It is not uncommon to see a specialty contact lens patient for several visits. Each time this patient was refit, the choice was made to go to different diameters and types of lenses, yet still fit with a larger diameter considering topography. It is important to learn the different aspects of specialty lenses, especially those with any proprietary parameters, such as flattening peripheral curve systems, optic zone parameters, availability of quadrant-specific alterations, and toricity options. These added features can help the clinician to further customize lenses to achieve the best fit possible. It is also important to move on to a different lens when the current one is not working for the patient, and change materials when sudden depositing issues arise. The incident with the disloged left contact lens was particularly disturbing to both the patient and the practitioner in that the corneal health was compromised for a time and the fitting process further delayed. Although the abrasion was surprisingly large, the patient reported only slight irritation or pain most likely due to decreased corneal sensitivity that often occurs in conditions such as keratoconus. The patient’s compliance with instilling drops and abstaining from contact lens wear were key in the healing process. The patient was motivated by the clear vision with gas permeable lenses that she had not experienced previously with soft toric contact lenses. Also important was that the patient was extensively educated at more than one visit regarding the nature of her 25 AMO Resident Most Challenging Contact Lens Case Catherine Pannebaker, O.D. ocular condition, and the possibility for multiple visits since had not been previously fit into gas permeable contact lenses prior to visiting the clinic. An additional skill that can be important on occasion is the ability to modify contact lenses in the office. This procedure of course requires not only the proper equipment, but adequate training so that the contact lenses are not damaged in the modification process. When performed properly, in-office modification can enable the patient to leave with contact lenses rather than having to place yet another order with a lab. It is important to properly clean lenses following modification to ensure proper wettability. Finally, it is important to educate patients on cleaning systems options. If onestep solution systems prove inadequate, a multi-step system may be necessary to ensure proper cleaning and good comfort of the lenses. In conclusion, it can be very challenging, yet very rewarding to properly fit keratoconus patients with gas permeable contact lenses. In addition to proper training on fitting and lens options, it is important to educate the patient about their condition and the possibility of multiple visits – especially with patients who are fit for the first time. Patients can experience an improvement in vision and therefore lifestyle when fit properly with gas permeable contact lenses. 26 AMO Resident Most Challenging Contact Lens Case Catherine Pannebaker, O.D. References 1. Rabinowitz, Yaron. Keratoconus. Survey of Ophthalmology (1998) 42:297-319. 2. Kinney, M. Christina. The Cascade Hypothesis of Keratoconus. Contact Lens & Anterior Eye (2003) 26:139-46. 3. Lema, Isabel. Inflammatory Molecules in the Tears of Patients with Keratoconus. Ophthalmology (2005) 112:654-659. 4. Rabinowitz, Yaron. 1st Annual Global Keratoconus Congress. Lecture in Las Vegas, Nevada, on January 27, 2007. 5. Zadnik, Karla and Joseph Barr et al. Baseline Findings in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study. Invest Ophthalmol Vis Sci (1998) 39:2537-2546. 6. Catania, Louis. Primary Care of the Anterior Segment, Second Edition. East Norwalk: Appleton & Lange; 1995, p. 266. 7. Riordan-Eva, Paul. Vaughan and Asbury’s General Ophthalmology. McGrawHill Professional; 2004, p. 144. 8. Gustavo de Souza et al. Identification of 491 Proteins in the Tear Fluid Proteome Reveals a Large Number of Proteases and Protease Inhibitors. Genome Biology. (2006) 7:R72. 9. Kijlstra A, Kuizenga A. Analysis and function of the human tear proteins. Adv Exp Med Biol (1994) 350:299-308. 10. Teng, CC. Electron microscope study of the pathology of keratoconus: Part I. Am J Ophthalmol (1963) 55:18-47. 11. Jongebloed, WL and JF Worst. The keratoconus epithelium studies by SEM. Doc Ophthalmol (1987) 67:171-81. 12. Jongebloed WL et al. Keratoconus morphology and cell dystrophy: a SEM study. Doc Ophthalmol (1989) 72:403-9. 13. Sawaguchi, S et al. Three dimensional scanning electron microscope study of keratoconus corneas. Arch Ophthalmol (1998) 116:62-8. 14. Dogru, Murat et al. Tear function and ocular surface changes in keratoconus. Ophthalmology (2003) 110:1110-18. 15. Stedman’s Medical Dictionary, 28th Edition. Lippincott Williams & Wilkins, 2000. 16. Ramamoorthy, P. Mucins, contact lens wear and dry eye – a review. Submitted and accepted for publication in Optometry and Vision Science, 2007. 17. Li, X et al. Two-stage genome-wide linkage scan in keratoconus sib pair families. Invest Ophthalmol Vis Sci. (2006) Sep; 47(9):3791-5. 18. Bechara, SJ et al. Keratoconus in two pairs of identical twins. Cornea (1996) 15:90-93. 19. McMahon, TT et al. Discordance for keratoconus in two pairs of monozygotic twins. Cornea (1999) 18:444-51. 20. Thompson, JS and MW Thompson. Twins in medical genetics. In: Thompson JS, Thompson, MW (eds). Genetics in Medicine. Philadelphia: WB Saunders, 1986. 21. Wang, Y et al. Genetic epidemiological study of keratoconus: evidence for major gene determination. Am J Med Genet (2000) 22:122-125. 27 AMO Resident Most Challenging Contact Lens Case Catherine Pannebaker, O.D. 22. Forstot, SL et al. Familial keratoconus. Am J Ophthalmol (1998) 105:92-93. 23. Falls, HF and AW Allen. Dominantly inherited keratoconus. J Hum Genet. (1969) 17:317-324. 24. Rabinowitz, Y et al. Computer-assisted corneal topography in keratoconus. Refract Corneal Surg (1989) 5:400-8. 25. Rabinowitz, Y et al. Molecular genetic analysis in autosomal dominant keratoconus. Cornea (1992) 11:302-8. 26. Edwards, Matthew et al. The genetics of keratoconus. Clin Experiment Ophthalmol. (2001) Dec; 29(6):345-51. 27. Beardsley, TL et al. An association of keratoconus and mitral valve prolapse. Ophthalmology (1982) 89:35-7. 28. Shariff, KW et al. Presence of mitral valve prolapse in keratoconus patients. J. R. Soc Med (1992) 85:446-8 29. Tang, Y et al. Genomewide linkage scan in a multi-generation caucasian pedigree identifies a novel locus for keratoconus on chromosome 5q14.3-q21.1 Genet Med. (2005) 7:397-405. 30. Fullerton, J et al. Identity-by-descent approach to gene localisation in eight individuals affected by keratoconus from north-west Tasmania, Australia. Hum Genet (2002) 110:462-470. 31. Rabinowitz, YS et al. IOVS (1999) 40: ARVO Abstract 2975. 32. Udar, N et al. SOD1: a candidate gene for keratoconus. Invest Ophthalmol Vis Sci. (2006) 47:3345-51. 33. Heon, E et al. VSX1: a gene for posterior polymorphous dystrophy and keratoconus. Hum Mol Genet. (2002) 11:1029-36. 34. Biscelgia, L et al. VSX1 mutational analysis in a series of italian patients affected by keratoconus: detection of a novel mutation. Invest Ophthalmol Vis Sci. (2005) 46:39-45. 35. Aldave, A et al. No VSX1 gene mutations associated with keratoconus. Invest Ophthalmol Vis Sci. (2006) 47:2820-22. 36. Lema, Isabel and Juan Durán. Inflammatory molecules in the tears of patients with keratoconus. Ophthalmology (2005) 112:654-59. 37. Kemp, EG and CL Lewis. Immunoglobulin patterns in keratoconus with particular reference to total and specific IgE levels. Br J Ophthalmol (1982) 66:717-20. 38. Rahi, A et al. Keratoconus and coexisting atopic disease. Br J Ophthalmol (1977) 61:761-4. 39. Collier, Simon. Is the corneal degradation in keratoconus caused by matrixmetalloproteinases? Clin Experiment Ophthalmol (2001) 29:340-4. 40. Fini, ME et al. Collagenolytic/gelatinolytic metalloproteinases in normal and keratoconus corneas. Curr Eye Res (1992) 849-62. 41. Kenny, MC et al. Localization of TIMP-1, TIMP-2, TIMP-3, gelatinase A and gelatinase B in pathological human corneas. Curr Eye Res (1998) 17:238-46. 42. Zhou, L et al. Expression of degradative enzymes and protease inhibitors in corneas with keratoconus. Invest Ophthalmol Vis Sci (1998) 39:1117-24. 28 AMO Resident Most Challenging Contact Lens Case Catherine Pannebaker, O.D. 43. Fabre, EJ et al. Binding sites for human interleukin 1 alpha, gamma interferon and tumor necrosis factor on cultured fibroblasts of normal cornea and keratoconus. Curr Eye Res (1991) 10:585-92. 44. Li, D and SC Pflugfelder. Matrix Metalloproteinases in corneal inflammation. Ocul Surf (2005) 3:S198-202. 45. Collier, SA et al. Expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) and MMP-2 in normal and keratoconus corneas. Curr Eye Res (2000) 21:662-8. 46. Ohuchi, E et al. Membrane type 1 matrix metalloproteinase digests interstitial collagens and other extracellular matrix macromolecules. J Biol Chem (1997) 272:2446-51. 47. D’Ortho, M-P et al. Membrane-type matrix metalloproteinases 1 and 2 exhibit broad spectrum proteolytic capacities comparable to many matrix metalloproteinases. Eur J Biochem (1997) 250:751-7. 48. Abalain, JH et al. Levels of collagen degradation products (Telopeptides) in the tear film of patients with Keratoconus. Cornea (2000) 19:474-76. 49. Kenney, M Christina and Donald Brown. The Cascade Hypothesis of Keratoconus. Cont Lens Anterior Eye (2003) 26:139-46. 50. Brown, DJ et al. Elements of the nitric oxide pathway can degrade TIMP-1 and increase gelatinase activity. Mol Vis (2004) 10:281-8. 51. Sawaguchi, S et al. Alpha-1 proteinase inhibitor levels in keratoconus. Exp Eye Res (1990) 50:549-54. 52. Matthews, Fiona et al. Changes in the balance of the tissue inhibitor of matrix metalloproteinases (TIMPs)-1 and -3 may promote keratocyte apoptosis in keratoconus. Exp Eye Res (2007) 84:1125-34. 53. Gondhowiardjo, TD and NJ van Haeringen. Corneal aldehyde dehydrogenase glutathione reductase, and glutathione S-tranferase in pathologic corneas. Cornea (1993) 12:310-14. 54. Gondhowiardjo TD et al. Analysis of corneal aldehyde dehydrogenase patterns in pathologic corneas. Cornea (1993) 12:146-54. 55. Twa, Michael. Lecture to third year optometry students at The Ohio State University College of Optometry, Winter Quarter, 2007. 29