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Pellucid Marginal Degeneration with Intacs® and Corneal Collagen Cross-linking: Brad Thomas Cunningham, OD, FSLS

Background

A 36-year-old Hispanic male, presented in the optometry clinic for a medical contact lens evaluation due to presumed advanced keratoconus (KC) in both eyes. This patient was medically retired in 2009 from the Army due to his diagnosis of advancing KC and worsening vision. The patient’s last eye examination was a medical contact lens evaluation for his prosthetic replacement of the ocular surface ecosystem (PROSE) lenses fit by another provider. These particular lenses are highly modifiable sclerals by BostonSight®. These lenses are also unique in that only trained providers that attended the Massachusetts nine-week clinical fellowship may fit these lenses. PROSE lenses may or may not be partially covered by insurance, and cost varies depending on the site that provides them.

Approximately six months prior to his initial appointment, the patient underwent significant corneal surgery. At that time, in addition to scleral lenses, the patient was properly educated by his team of eye doctors about other procedures including the option of Intacs and corneal collagen cross-linking (CXL). Although he appeared to be pleased with the results of the PROSE lenses, he became intolerant of the scleral contacts and wanted to avoid penetrating keratoplasty procedures. The patient made every effort to prevent any corneal progression. He created fundraising website account to raise money since the procedures were not covered by his insurance. After several months, he raised enough funds and received two Intacs OU on and CXL with riboflavin OU two months later. This elective, off-label procedure was conducted by a private practice corneal ophthalmologist who the patient was referred to by his assigned military corneal specialist.

The patient’s pre-operative vision was best corrected to OD 20/25 and OS 20/20. The patient’s Pentacam (Figures 1a and 1b) showed highly irregular astigmatism caused by advanced Pellucid Marginal Degeneration (PMD). Severe steepening >60D and apical thinning was observed in both eyes. The pre-operative comprehensive dilated examination found no significant posterior segment findings.

The patient’s post-operative best corrected acuity was OD 20/20- and OS 20/20. His last eye examination was approximately six months prior with his military corneal specialist and no additional significant finding was reported.

Figure 1a: Pre-operative OD Pentacam

Figure 1b: Pre-operative OS topography

His medical and family history was unremarkable. No other family member was known to suffer from KC or any corneal ectasia. The patient reported good vision with the PROSE lenses; however, he complained “seeing the fluid” and when light emerges from the sides he becomes distracted. As the patient became intolerant of the lenses, he was offered to be fit with a different scleral lens design. He accepted and was scheduled for a new fitting.

Test Procedures, Fitting/Refitting, Design, and Ordering

Visit #1: Initial Visit

Uncorrected Visual Acuity

OD: 20/100 pinholed to 20/30 (distance), 20/30 (near)
OS: 20/400 pinholed to 20/100 (distance), 20/50 (near)

Manifest Refraction

OD: -5.25 -5.50 x030 (20/30-2)
OS: -5.75 -4.50 x056 (20/20-1)

The patient reported uncomfortable distortion of all fine detail and ghosting of the letters in both eyes with best spectacle correction.

Pupils were equally round and reactive to light with no afferent pupil defect observed OU. Confrontation fields were full to finger count OU. His extraocular muscles were unrestricted in all gazes and cover test demonstrated orthophoria at distance and 5 prism diopters of exophoria at near. His intraocular pressure was 10 mmHg OD and 8 mmHg OS using non-contact tonometry at 1:14 pm.

Anterior Segment Examination

Slit lamp examination revealed 1+ conjunctival injection of both eyes, significant inferior stromal thinning with striae and small mild round scarring slightly inferior of both corneas. The four Intacs appeared well placed at one and seven o’clock OD and five and eleven o’clock OS. No signs of complication observed. About 1 mm of temporal limbal neovascularization of encroachment in the left eye only was observed. Both eyes exhibited scattered 1+ punctate epithelial keratopathy with fluorescein. Lids and lashes were clear; anterior chambers were deep and quiet. Irises were flat and brown and lenses were clear in both eyes.

Posterior Segment Evaluation

Using a 90D lens was used to view the posterior segment both eyes. The vitreous was clear and optic nerves were healthy with cup to disc ratios of 0.30 by 0.30. His maculae appeared normal with good foveal reflexes and vessels of normal structure, course and caliber. Posterior poles were flat, intact and within normal limits.

OCULUS Pentacam

Pentacam scan (Figures 2a and 2b) was taken of each eye and initially it may appear to have the same inferior thinning and steepening as seen in the prior pre-operative scans. However, post-operatively the corneas had altered significantly. His right keratometry readings went from 53.3/48.8 @ 058 to 64.1/59.4 @ 157 and left went from 54.0/43.1 @ 103 to 56.6/56.3 @ 179. The thinnest corneal reading went from 348 mm to 365 mm in the right eye and 452 mm to 418 mm in the left eye. Both sets of INTACS and CXL essentially flipped the cylinder correction; therefore, the overall astigmatism was dramatically reduced by 10.6 D in the left eye. However, the right eye increased slightly by 0.2 D. Interestingly, the thinnest corneal measurement increased by 17 mm in the right eye but decreased by 34 mm in the left eye after CXL. Also noted, the overall anterior chamber volume measurements decreased from 239 mm3 to 218 mm3 in the right eye and 244 mm3 to 217 mm3 in the left eye.

Figure 2a: Post-operative OD Pentacam

Figure 2b: Post-operative OS Pentacam

He was diagnosed with advanced PMD with successful Intacs and CXL due to the crab-claw corneal topographies, significant inferior stromal thinning with striae and small mild round scarring slightly inferior of both corneas. Although KC and PMD are thought to be two separate diagnoses, there has been no evidence supporting these are, in fact, different ectatic processes.

Medically indicated scleral lenses were recommended for the patient to improve visual acuity, comfort, and therapeutically reduce corneal dryness. Spectacles were an inferior option. Scleral lenses were warranted due to the severe state of his disease and to complete the treatment recommended by the corneal specialists. Although custom soft lenses, piggyback systems, or hybrid lenses would also be an option, the patient preferred to continue with scleral GP lenses.

Scleral Lens Fitting

Diagnostic Lens Selection

The patient was refit into Zenlens sclerals. Following the Zenlens fitting guidelines, due to the patient’s measured HVID being greater than 11.8 mm OU, the larger, 17mm diagnostic lens was used. As the patient’s corneas were steeper in the periphery, the oblate lens design was selected. The lenses were filled with preservative-free saline solution and applied onto the patient’s eyes using a plunger without complications or bubbles

Initial Diagnostic Lenses: Zenlens Oblate

OD: Z-21: BC: 9.70 mm, Dia: 17.0 mm, Pwr: -2.00, SAG: 4800 mm, PC: Standard
OS: Z-21: BC: 9.70 mm, Dia: 17.0 mm, Pwr: -2.00, SAG: 4800 mm, PC: Standard

The lenses were assessed after approximately five minutes. Both of the lenses demonstrated inferior mid-peripheral bearing with the right lens appearing to have slightly less clearance. Inadequate sagittal depth of the lenses directed the second trial lenses to be deeper.

Second Diagnostic Lenses: Zenlens Oblate

OD: Z-23: BC: 8.50 mm, Dia: 17.0 mm, Pwr: -2.00, SAG: 5400 mm, PC: Standard
OS: Z-24: BC: 7.90 mm, Dia: 17.0 mm, Pwr: -2.00, SAG: 5700 mm, PC: Standard

The lenses were evaluated and exhibited slight inferior centration with improved central and mid-peripheral clearance. The estimated clearance over the steepest corneal elevation was 160 mm OD and 264 mm OS. Both eyes minimally cleared the limbus without touch and displayed tight horizontal edges with mild compression and blanching of the nasal conjunctiva. Over-refraction: -2.75 -1.00 x150 to 20/20 OD and -5.25DS to 20/20. 15 minutes after application, anterior segment ocular coherence tomography (AS-OCT) was acquired (Figures 3a and 3b).

Figure 3a: AS-OCT showing 160 mm clearance, right eye

Figure 3b: AS-OCT showing 264 mm clearance, left eye

The patient was impressed with the quality of the vision and increase in overall comfort in comparison to the PROSE lens. After allowing the lens to settle for over 45 minutes, the lenses were assessed again. Due to minimal sagittal depth on the right eye, the vault was increased by 300 mm that made the total SAG 5700 mm. The Zenlens Smart Curve allows independent changes to the sagittal depth without changing the base curve. The minimal horizontal limbal clearance (Figure 5a) and the slight inferior decentration was addressed by adding toric peripheral curves and increasing the limbal curve by 150 mm in each eye. The power of the lenses was calculated using the over-refraction. The goal was to achieve complete vault over the entire cornea with a target of 250-350 mm over the steepest corneal elevation, adequate limbal clearance 360 degrees, good centration, minimal to no movement, adequate landing, and optimal vision correction.

Final Lens Order

OD: Zenlens, BC: 8.50 mm, Dia: 17.0 mm, Pwr: -4.75 -1.00 x150, SAG: 5700 mm, LZ: Standard PC: flat 3 horizontal / steep 1 vertical, Boston XO material, single dot @ 6 o’clock, blue tint

OS: Zenlens, BC: 7.90 mm, Dia: 17.0 mm, Pwr: -7.00, SAG: 5700 mm, LZ: Standard, PC: flat 4 horizontal / steep 1 vertical, Boston XO material, double dot OS @ 6 o’clock, blue tint

The patient was scheduled to return in one month for a contact lens evaluation with expectations to dispense. As the patient demonstrated good technique and had experience with sclerals, no additional training was necessary.

Patient Consultation and Education

Visit #2: Dispense Appointment

Scleral Lens Evaluation

The new lenses were filled with preservative-free saline solution and applied using a plunger without complications or bubbles. They were assessed after approximately five minutes. The patient reported acceptable lens comfort and vision. The visual acuity was measured to be 20/20 in the right and left eye and 20/15- with both eyes open. An over-refraction was completed and was found to be PL -0.50 x005 in the right eye and PL -0.50 x020 in the left eye providing no significant visual improvement.

Slit lamp evaluation revealed both lenses to have adequate centration with an estimated central clearance of approximately 356 mm in the right eye and 248 mm in the left eye (Figures 4a and 4b). Both lenses cleared the limbus (Figures 5b) and provided acceptable edge alignment without any signs of compression or impingement. When manually rotated, the lenses returned back to the original position with the dots at the desired position due to the toricity of the lenses. Both lenses were found to be acceptable for dispensing as the fit, feel, and vision were appropriate.

Figure 4a: AS-OCT showing 356 mm clearance, right eye

Figure 4b: AS-OCT showing 248 mm clearance, left eye

Figure 5a: Insufficient limbal clearance with diagnostic lens, left eye

Figure 5b: Appropriate limbal clearance with ordered lens, left eye

Application, Removal, and Care Education

Patient education concerning wear and care was provided. Peroxide-based cleaning solutions and non-preserved saline solution for lens application was recommended. The patient was provided a lens care kit that included application and removal plungers, a mirror with stand, a pen light to look for bubbles after insertion, and a large scleral lens case for over-night cleaning using Clear CareÒ. Proper application and removal education was reinforced and the patient was instructed to slowly increase the wear time of the lenses over the next several weeks, not to exceed twelve hours until the scheduled follow up in three weeks.

Follow-up Care and Final Outcome

Visit #3: Three Week Follow-Up Visit

The patient presented in the clinic for his contact lens progress evaluation. He reported great vision and comfort was great in both eyes with no issues managing the lenses. He specifically expressed that he liked these lenses the best due to the vision, comfort, and was able to use them full time for at least twelve hours per day.

The visual acuity was measured to be 20/20+ in the right and left eye and 20/15 with both eyes open. There was no significant over-refraction. Upon slit lamp evaluation, both lenses revealed adequate centration, an estimated central clearance over 240 mm, and cleared the limbus. The lenses provided acceptable edge alignment without any signs of compression or impingement.

The patient’s anterior segment revealed no punctate epithelial keratopathy and no other remarkable ocular findings were observed. The patient was instructed that he may continue wearing the lenses during the day but never to sleep or swim in them. It was requested the patient be scheduled for a one-month follow-up visit to assess the lenses.

Visit #4: Three Month Follow-Up Visit

The patient presented in the clinic three months later for a contact lens progress evaluation. He reported his vision and comfort was great in both eyes with no issues managing the lenses. He has been using them full time for at least twelve hours per day.

The visual acuity was measured to be 20/20 in the right and left eye and 20/15- with both eyes open, and over-refraction was plano in each eye. Upon slit lamp evaluation, both lenses revealed excellent centration. Both lenses showed an estimated central clearance over 240 mm and cleared the limbus. Both lenses provided acceptable edge alignment without any signs of compression or impingement (Fig. 6).

No punctate epithelial keratopathy or new ocular findings were observed compared to the last examination. The patient was instructed that he may continue to wear the lenses full time and was scheduled for a one month follow up visit.

Figure 6: Scleral lenses on the right and left eyes

Visit #5: One Month Follow-Up Visit

The patient presented in the clinic in one month for contact lens evaluation. He reported his vision and comfort was great in both eyes with no issues managing the lenses. He added that he has been using them full time for at least twelve hours per day.

The visual acuity was 20/20+ in the right and left eye and 20/15 with both eyes open. An over-refraction was completed and was found to be plano. Upon slit lamp evaluation, both lenses revealed excellent centration. Complete corneal and limbal clearance was observed. Both lenses provided acceptable edge alignment without any signs of compression or impingement.

Anterior segment revealed 1+ conjunctival injection of both eyes, significant inferior stromal thinning with striae and small mild round scaring slightly inferior of both corneas. The Intacs in both eyes appeared well placed and without signs of complication. Temporal limbal neovascularization measured to be 1 mm of encroachment of the left eye only were observed. No punctate epithelial keratopathy nor any other remarkable ocular findings were observed. The patient was instructed to continue utilizing the lenses and wear them full time during the day but never to sleep or swim in them.

No alterations were necessary to the lenses as there were no clinically significant new findings or changes since the last examination. His contact lens prescription was finalized and was instructed to follow up in six months for a comprehensive eye examination and evaluation of the scleral lenses.

Discussion/Alternative Management Options

Pellucid marginal degeneration (PMD) is a rare, progressive, and degenerative corneal disease typically characterized by peripheral, bilateral, and inferior ectasia producing a crescent shape.1 PMD, while rare, is the second most common non-inflammatory corneal thinning disorder behind keratoconus.1, 8, 9 It has been found more commonly in males and appears between the second and fifth decade of life showing no signs of ethnicity predilection.1, 8 It is possible PMD is more common than reported because of the lack of practitioners reporting the difference. PMD is commonly diagnosed as KC or a version of KC; therefore it is not well differentiated.1, 9 Although these conditions are clinically different, they may be from the same ectatic process that is not yet fully understood.

KC is a developmental anomaly in which a part of the cornea becomes thinner and bulges forward in a cone-shaped fashion as a result of non-inflammatory stromal thinning.2 KC is predominantly bilateral (90%) and according to recent studies demonstrates a prevalence of 2.3%.2,3 The CLEK study found the genetic predisposition of KC to be at 13.5% whereas other studies found it to be between 6-10%.2,3 This indicates most of those found having KC have no known association with the disease and that we have not yet truly determined the cause. Regardless, KC and PMD are complex diseases where eye rubbing has been associated with KC and is considered an additive environmental factor.

Once identified, PMD and KC have similar treatment options. It is typical for less severe cases of PMD to be treated with spectacles and toric soft contact lenses. More severe PMD patients may require more specialized options such as custom soft contact lenses, rigid gas-permeable (GP) lenses, or hybrid contact lenses. Depending on the severity of the corneal thinning, the clarity of the cornea and the amount of irregular astigmatism, the visual potential and quality of vision can range widely. Monocular diplopia, ghosting, blurring, and image distortion are all complications of astigmatism that may arise from PMD. These complications may all be mitigated through specialty scleral GPs that offer excellent oxygen permeability to maintain the health of the cornea. Corneal GPs are not typically used for PMD due to the inferior peripheral steepening that the edges of the GP may land on. This may cause excessive movement, inhibit comfort, and increase the potential of corneal scarring.

Scleral GPs that are fit appropriately provide 360 degrees of corneal and limbal clearance and a vault that rests on the conjunctiva and sclera.12 Due to the size of the lens and the location of the landing zone, the lens awareness or irritation is minimal. As observed with this patient, the scleral lenses provided optimal vision correction that could not be obtained with spectacles. The lenses provided excellent dry eye therapy and resolved the punctate epithelial keratopathy completely. The patient had no discomfort and was able to wear the lenses all day.  

Poor fitting scleral GPs may cause complications. Microbial keratitis, corneal keratitis and corneal scarring are among the rare complications reported.12 Lens fogging, or mid-day haze is a more common complication that is associated with ocular surface disease, a poorly fitting lens, or debris within the tear lens. The ocular surface disease may be improved by continuous wear of scleral lenses. Otherwise, improving the fit by aligning the scleral landing zone and ensuring no bubbles or debris on insertion can prevent fogging. Extremely poor fitting scleral GPs may cause corneal edema and neovascularization. However, it has been reported that risk of neovascularization may reduce with the use of properly fitting scleral lenses, which was the intent for the patient.12

In severe PMD or KC, surgical treatments may be warranted. In the most severe cases, penetrating keratoplasties (PKP) have shown great success. Although, they typically require spectacle or contact lens correction afterwards and there is a clinically significant risk of graft rejection.13, 14 According to the Corneal Donor Study (CDS), the graft age was not found to be a rejection factor. The 10-year graft failure rate was 21% from all causes, 37% in cases with pseudophakic or aphakic corneal edema, and 20% in cases with Fuchs’ dystrophy. Furthermore, in cases with prior glaucoma surgery, a graft failure rate of 58% was found versus 22% with no history of glaucoma.14

The United States Federal Drug Administration (FDA) approval of KC treatment using corneal cross-linking (CXL) in April 2016 has shown excellent promise of improving the visual potential of patients with this progressive disease.4, 13 CXL with riboflavin and ultraviolet A is a technique used to strengthen corneal tissue with riboflavin as a photosensitizer and ultraviolet A to increase the formation of stromal collagen cross-links by photosensitized oxidation.15 Riboflavin (vitamin B2) has a dual function of acting as a photosensitizer for the production of oxygen free radicals, which induce physical cross-linking of collagen, and it gives a protective effect by absorbing 90% of the UV-A (370 nm) irradiation thereby preventing damage to deeper ocular structures.16

The FDA has approved this procedure that typically begins with corneal epithelial debridement. The Dresden Protocol has been named a standard corneal cross-linking procedure.4 The protocol includes the installation of 0.1% riboflavin solution in 20% dextran for 30 minutes with drops every 3-5 minutes, followed by UV-A irradiation with 3mW/cm2 for 30 minutes for a total dose of 5.4 J/cm2. A bandage soft contact lens is then utilized to aid healing and minimize pain in conjunction with a topical antibiotic and anti-inflammatory post-surgical regiment. There are numerous protocols using different riboflavin formulations (trans-epithelial, nondextran, and different concentrations of riboflavin) and different levels of UV-A illumination being studied.4, 15, 16 CXL is being assessed to be used for other conditions, such as post-LASIK regression minimization, treatment of infections keratitis, corneal melts, Acanthamoeba cysts, and post-thermal keratoplasty stabilization.4, 15, 16

Some CXL studies reported associated complications and limitations. For example, it is not recommended in cases with a corneal thickness of 400 nm or less because of increased risk of corneal endothelial cell damage. 4, 20 Also, postoperative microbial keratitis, corneal haze, corneal endothelial damage, sterile corneal stromal damage, herpes simplex virus reactivation, and treatment failure/keratoconic progression are among the reported of complications of CXL.4, 20 It has been shown that CXL is able to reduce corneal steepening, improve refractive error by minimizing irregular astigmatism, can inhibit the progression of corneal ectasia with a low risk of complications, and reduce the need for keratoplasties.4, 13, 15, 16, 20

Another surgical option approved by the FDA in July 2004 that the patient took advantage of is termed intra-stromal corneal ring segments or Intacs. Clear crescent plastic rings are inserted into the stroma on a specific steep axis to flatten the overall corneal curvature.17 As observed with this patient, this was an additive surgery due to his severe amount of astigmatism. There are many versions of protocols used to apply INTACS. Due to complications observed over time, newer procedures have been applied. For example, the use of IntraLase laser created channels have reduced the complications of false channels, perforations, and may provide very precise and accurate channels as compared to a manual approach.17, 21 Another protocol suggested two equal ring segments should be used for symmetric bow-tie patterns of ectasia or keratoconus and asymmetrical segments should be used for peripheral cones and the segment thickness should not exceed 50% of the thickness of the cornea.21 Postoperative microbial keratitis, peripheral corneal haze, peripheral corneal endothelial damage, sterile corneal stromal damage, and treatment failure/keratoconic progression are among the reported of complications of INTACS.17, 21, 22

One study documented long term (>5 years) results of KeraRings intracorneal ring implantation and concluded that KeraRings result in topographic and visual stability, delayed the progression of keratoconus and, at minimum, postponed the need for keratoplasty.21 Of note, regression of visual stability and progression of keratoconus has been observed a year or longer after Intacs. It was concluded that ectatic corneas with high irregularity and a pronounced conic protrusion may be poor candidates for intracorneal ring segment implantation.21 Those with highly irregular and advanced ectasias may benefit from combined Intacs and CXL surgeries.21,22 Further evidence of this surgical combination is being evaluated and more long-term treatment strategies are recommended.22

Although the procedures for this patient were deemed successful by ophthalmology due to the lack of complications and reduction of corneal steepening, he still required contact lenses to achieve the best vision. Continued evaluation over the next several years will determine stabilization. With the addition of scleral contact lenses, he and his eye care team is hopeful these treatments will stabilize his PMD and prevent further ectatic corneal progression and prevent him from requiring some form of corneal transplant.

Although there is no cure for PMD or any of the versions of KC, it is our job and responsibility as primary care optometrists to do our best to manage the condition and associated refractive complications. Proper patient education, identification and treatment are critical to the prognosis and treatment outcome of PMD. To attempt to stabilize the condition and reduce the risk factors for loss of vision is paramount. Cases such as this demonstrate the usefulness of utilizing scleral gas permeable lenses over Intacs post CXL to provide optimal vision, comfort and therapy.

References

  1. Jinabhai A, Radhakrishnan H, O’Donnell C. Pellucid corneal marginal degeneration: A review. Contact Lens and Anterior Eye 2011;34(2): 56-63.
  2. Gordon-Shaag A, Millodot M, Shneor E. The epidemiology and etiology of keratoconus. Epidemiology 2012;70:1.
  3. Wagner H, et al. Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study: methods and findings to date. Contact Lens and Anterior Eye 2007;30(4):223-232.
  4. Raiskup-Wolf F, et al. Collagen crosslinking with riboflavin and ultraviolet-A light in keratoconus: long-term results. Journal of Cataract & Refractive Surgery 2008;34(5):796-801.
  5. Davidson AE, Hayes S, Hardcastle AJ, Tuft SJ. The pathogenesis of keratoconus. Eye 2014:28:189-195.
  6. Schuerch K, Tappeiner C, Frueh BE. Analysis of pseudoprogression after corneal cross‐linking in children with progressive keratoconus. Acta ophthalmologica 2016;94:7.
  7. Shovlin JP. Do I see keratoconus or PMD? How can we differentiate between these two similar ectatic diseases on corneal topography?. Review of Optometry 2005;142(4): 91-92.
  8. Jinabhai A, Radhakrishnan H, O’Donnell C. Pellucid corneal marginal degeneration: A review. Contact Lens and Anterior Eye 2011;34(2): 56-63.
  9. Nagy M, Vigvary L: Etiology of the pellucid marginal degeneration of the cornea. Klin Monatsbl Augenheilkd 161:604–611, 1972.
  10. Khan AO, et al. Pellucid marginal degeneration coexistent with cornea plana in one member of a family exhibiting a novel KERA mutation. British journal of ophthalmology 2005;89(11): 1538-1540.
  11. Barr JT, Wilson BS, Gordon MO, et al. Estimation of the incidence and factors predictive of corneal scarring in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study. Cornea 2006; 25: 16– 25.
  12. van der Worp, E. A Guide to Scleral Lens Fitting, Version 2.0. Pacific University. Available at: https://commons.pacificu.edu/mono/10/.
  13. Schornack M, Patel S. Scleral lenses in the management of keratoconus. Eye & Contact Lens 2010:1:39-44.
  14. Sugar A, et al. Factors associated with corneal graft survival in the cornea donor study. JAMA Ophthalmology 2015;133(3):246-254.
  15. McCall AS, Kraft S, Edelhauser HF, et al. Mechanisms of corneal tissue cross-linking in response to treatment with topical riboflavin and long-wavelength ultraviolet radiation (UVA) Invest Ophthalmol Vis Sci. 2010;51:129–138.
  16. Arbelaez MC, et al. Collagen cross-linking with riboflavin and ultraviolet-A light in keratoconus: One-year results. Oman journal of ophthalmology 2009;2(1):33.
  17. Kanellopoulos JA, et al. Modified intracorneal ring segment implantations (INTACS) for the management of moderate to advanced keratoconus: efficacy and complications. Cornea 2006;25(1):29-33.
  18. Paulus, Y. (2015, March 1). Pellucid Marginal Corneal Degeneration. Retrieved February 15th, 2017, from http://eyewiki.aao.org/pellucid_marginal_corneal_degeneration
  19. “pellucidity”. Online Etymology Dictionary. Douglas Harper, Historian. 7 May. 2017. <Dictionary.com http://www.dictionary.com/browse/pellucidity>.
  20. Hashemi, Hassan, et al. Corneal collagen cross-linking with riboflavin and ultraviolet a irradiation for keratoconus: long-term results. Ophthalmology 2013;120(8):1515-1520.
  21. Coskunseven E, et al. Complications of intrastromal corneal ring segment implantation using a femtosecond laser for channel creation: a survey of 850 eyes with keratoconus. Acta ophthalmologica 2011;89(1):54-57.
  22. Bromley JG, Randleman JB. Treatment strategies for corneal ectasia. Current opinion in ophthalmology 2010;21(4):255.

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