Corneal Implants and Inlays





Introduction


Presbyopic corneal inlays are implanted in the corneal stromal tissue to increase the eye’s depth of focus and to correct presbyopia. The initial steps toward the development of present-day corneal inlays started with the use of alloplastic lenticules by José Barraquer in 1949, when he described the inclusion of a lenticule within the corneal stroma to modify ametropia. A newer generation of corneal inlays offers great potential for the treatment of presbyopia in a minimally invasive way by using the recent advances in femtosecond (FS) laser technology and more advanced inlay designs.


Barraquer speculated that stromal lenticules would modify both the anterior curvature of the cornea and the cornea’s index of refraction. He experimented first with Flint glass lenses and later used transparent plastic (Plexiglas). Because all of the lenses were poorly tolerated by the cornea, he abandoned the use of alloplastic materials.


The implants that Barraquer initially experimented with resulted in anterior stromal necrosis, followed by extrusion of the implants. However, the posterior layer of the cornea, situated behind the lenticule, remained transparent. In their search for an ideal intracorneal lens, Choyce, Belau, Knowles, Dohlman, Steinert and others experimented with different lens materials ( Table 38.1 ). In 1961, Knowles investigated three polymers: polyethylene, polyvinylidine, and polypropylene. He consistently observed a degenerative process external to the plastic membrane regardless of the material or depth of placement in rabbit eyes. Most of the eyes developed a dense haze, frequently followed by a dimple or crater in the epithelial surface, with microscopic degeneration and disappearance of the substantia propria ( Fig. 38.1 ). The absence of inflammation and the sharp localization of the defect anterior to the implant suggested the absence of toxic reaction to the plastics used. Knowles attributed the anterior stromal degeneration and crater formation to one of three causes: lack of nutrients from the aqueous humor, accumulation of toxic metabolites, or relative drying of the cornea lying anterior to the plastic.



TABLE 38.1

Materials Used for Alloplastic Intracorneal Lenses























Flint glass
Plexiglas
Polyethylene
Polyvinylidine
Polypropylene
Silicone
Glyceryl methacrylate
Hydroxyethyl methacrylate
Polysulfone
Polymethylmethacrylate



Fig. 38.1


Histologic appearance of a crater in a formative stage, 32 days after insertion of the implant.

(From Knowles WF. Effect of intralamellar plastic membranes on corneal physiology. Am J Ophthalmol . 1961;51:1146–1156, with permission from Elsevier.)


Belau et al. attempted to determine the most suitable material for an intracorneal lens, the most suitable surgical technique for its placement, and the change in refraction of the eye produced by the lens. The following materials were used: polymethylmethacrylate (PMMA); PMMA coated with silicon monoxide; Dow Corning XR-63428, a silicone formed by heating and curing a mixture of equal parts of constituents A and B ; and optical crown glass. Although silicone was the most suitable of the various materials used, the PMMA lens was generally well accepted. The best surgical techniques involved the use of a corneolimbal incision with or without a conjunctival flap. Most important, the finding of the study suggests a linear relation that would, with adequate data, make the refractive change predictable.


In 1967, Dohlman et al. were the first to examine hydrogel intracorneal inclusions. By implanting discs of glyceryl methacrylate (GMA), containing 88% water, within the corneas of cats and rabbits, the authors investigated the tolerance of the stroma to GMA. The lenses were 4 mm in diameter, with thickness ranging from 0.19 to 0.57 mm. There was little or no inflammatory reaction in rabbit corneas, but the membranes slowly extruded within 3 months of the operation. The authors believed that this was related to the water permeability of GMA rather than to the toxicity of the lens material. The GMA implant was well tolerated in the cat cornea for the 11-month follow-up.


In 1981, McCarey and Andrews demonstrated that high-water-content hydrogels were biologically compatible in rabbits. They also reported that the hydrogel lenticular implant was successful as a refractive keratoplasty implant material. The lenticules used were Permalens (Perfilcon-A), with a 6-mm diameter and a 0.23-mm thickness. Binder et al., using various hydrogel lenses (containing 38%–79% water), have shown these materials to be compatible in nonhuman primates.


In 1992, Werblin et al. reported the first human experience with the myopic Permalens hydrogel implantable collamer lens (ICL; 18-month follow-up). All surgeries were performed by Barraquer in Bogotá, Colombia. Excellent corneal clarity was reported throughout the follow-up period ( Fig. 38.2 ). No decentration of the lenticule following implantation was observed. Corrections of up to −13 diopters (D) were achieved. Corrections deviated from the predicted correction by a mean of −5.00 ± −2.10 D (range, −2.80 to −8.00 D). Visual recovery was rapid, usually achieving maximum acuity within 1 month. The major problem was the significant undercorrection of the preoperative refraction.




Fig. 38.2


Hydrogel implantable collamer lens in a human subject 4 months postoperatively. The hydrogel appears as an optically void area at midstromal depth (dark arrows) . One or two interface opacities can be seen (open arrow) , but the overall appearance of the cornea is very clear.

(From Werblin TP, Patel AS, Barraquer JI. Initial human experience with Permalens myopic hydrogel intracorneal lens implants. Refract Corneal Surg. 1992; 8(1):23–26, with permission from Slack, Inc.)


A longer follow-up was reported by Barraquer, in 1997, of five aphakic and five high myopic eyes with hydrogel implants. Corneal clarity was maintained after 6 years in all but one eye. Undercorrection was again observed by an average of 3.37 D ± 0.53 D at 1 month for aphakic eyes. No statistically significant difference was reported in the results of aphakic eyes at 1 month compared to 6 years postimplantation of the hydrogel ICLs. On the other hand, all myopic eyes showed continued regression of achieved correction at 1 month by an average of −7.06 ± 2.28 D in 72 months.


The current understanding of tolerance of intracorneal inlays is that many variables play important roles in the surgical outcomes of intrastromal corneal inlays. These include biocompatibility of the material used, diameter and thickness of the inlay, corneal depth at which the inlay is implanted, permeability of the inlay, pore number diameter, refractive index of the material used, power (diopters) and shape of the inlay, and the specific surgical technique used for inlay implantation. Determination of the predictability and long-term outcome of corneal inlay is of utmost importance. Intracorneal inlay material should not alter the posterior-to-anterior movement of water and nutrients. Furthermore, the implant should not interfere with the anterior-to-posterior movement of lactic acid from the epithelium. In addition, the stromal fluid pH, osmolarity, and stromal swelling pressures should not affect the stability of the lens material within the cornea.


Ideally, the refractive power correction should be derived from the optics of the implant, comparable to intraocular lens (IOL) diopteric power correction within the aqueous, and the surgical procedure should be simplified by using a corneal flap.




Principles of Corneal Inlays


There are three major refracting surfaces in the eye: the anterior corneal surface and the two surfaces of the crystalline lens. The effect of the posterior corneal surface is negligible because the difference in refractive index between corneal stroma and aqueous humor is insignificant. The cornea, which has a refractive power three times that of the crystalline lens (approximately +43 D compared with +19 D for the crystalline lens), is an extremely important refracting element in the eye. The greater refractive power of the cornea is due to the difference in refractive index between air (1.000) and cornea (1.376) compared with the refractive index between aqueous and vitreous humor (1.336) and lens (1.406).


Corneal inlays affect the refractive power of the cornea in three ways: by altering the radius of curvature of the anterior corneal surface, by altering the refractive index of the cornea, and by changing the depth of focus with small aperture optics. The corneal inlays that are available today are summarized in Table 38.2 .



TABLE 38.2

Corneal Inlays Commercially Available Today




















































Corneal Inlay Material Principle Diameter Thickness Weight Flap/Pocket Placement Centration Healing Time Possibility of Combination With Other Refractive Procedures Year of Development/Approval
KAMRA Polyvinylidene fluoride (PVDF) Small aperture inlay 3.8 mm (outer) 5 or 6 µm? Lighter than a grain of salt Visual axis within the corneal stroma (residual stromal bed: ≥ 250 µm below the pocket; minimum placement depth: 170–200 µm) 1.6 mm (Placement over the first Purkinje image) A few days to longer Combination with LASIK possible, peer-reviewed data available 2007
Raindrop near vision 80% water, made from hydrogel Corneal reshaping inlay; hyperprolate 2.0 mm 32 µm Under femtosecond-created flap, allowing for adherence (residual stromal bed: > 300 µm below the flap; minimum placement depth: 150 µm) Central overlight constricted pupil 1 day Combination with LASIK possible, peer-reviewed data available 2016
Flexivue microlens Hydrophilic, acrylic (Hydroxyethyl methacrylate and methyl methacrylate), contains an UV blocker Refractive corneal inlay 3.6 mm 15-20 µm Center of the cornea, like multifocal lens/stromal tunnel created through SMILE; placement depth 280–300 µm 1.6 mm (Placement over the first Purkinje image) Combination with cataract surgery, intrastromal pocket creation, possible, peer-reviewed data available

LASIK, Laser in-situ keratomileusis; SMILE, small-incision lenticle extraction.


Alloplastic materials whose refractive indexes approximate corneal stroma affect refraction only when used in combination with an anterior corneal flap. This causes a significant change in the anterior corneal curvature, thus providing the needed change in refraction.




FDA-Approved Corneal Inlays in Use


KAMRA Inlay ( )


The first corneal inlay to gain US Food and Drug Administration (FDA) approval for use in vision correction surgery in April 2015, KAMRA inlay is an extremely light (lighter than a grain of salt) 3.8-mm, round mini-contact lens–like opaque corneal inlay that has a 1.6-mm opening in the center with a thickness of 5 µm. It is made of proven biocompatible material called polyvinylidene fluoride (PVDF) that is often used in a wide variety of eye and other medical implants ( Fig. 38.3 ). It allows only focused light into the eye through the hole in the central aperture while obscuring the peripheral rays, thus increasing depth of focus. The depth of focus at a point increases the smaller the aperture gets. The KAMRA inlay has been optimized to provide the best depth of focus and image quality for the human eye. It is placed within the stroma in the FS laser–created pocket on the visual axis. The first Purkinje image provides the reference for the placement centration for the inlay. The implantation of the KAMRA inlay does not cause any topographic changes since the inlay is placed relatively deep within the cornea.




Fig. 38.3


KAMRA Inlay.


Although it does not affect distance vision, the KAMRA inlay is typically only implanted in the nondominant eye to provide near vision restoration without compromising the far and intermediate vision. This is done so that the combination of either the untouched eye or the eye corrected for great distance vision—in combination with the KAMRA implanted eye—can provide great near, intermediate, and distance vision by working together. The KAMRA inlay hopes to provide near, intermediate, and distance vision in a more stable, predictable and long-lasting way. The mechanism of how it facilitates accommodation in the presbyopic eye is shown in Fig. 38.4 . Further, the existence of 8400 laser-etched openings in the KAMRA inlay provide maximum breathability and health to the cornea by allowing oxygen, nutrients, and water to pass through. Each of these 8400 laser-etched openings is 5 to 11 µm in diameter and is spread throughout the inlay in a random fashion. Because of these designs allowing metabolic homeostasis, the KAMRA inlay is able to avoid complications such as corneal melting or decompensation. As the KAMRA inlay is often close to the visible size of the physiologic pupil diameter, it minimizes apparent anisocoria as well. The KAMRA inlay implantation procedure typically takes less than 15 minutes, without the need for any stitches. The healing time varies by patient, from as little as a few days to longer.


Fig. 38.4



(A) Ray tracing diagram of image formation in the presbyopic eye without any inlay






(A) Ray tracing diagram of image formation in the presbyopic eye without any inlay





The KAMRA website lists the following points as important for use in the United States:



  • 1.

    There may still be need for reading glasses after the KAMRA inlay implantation.


  • 2.

    Some complications that can occur after the KAMRA inlay implantation include refractive problems, such as blurred vision, glare, halos, color disturbances, contrast sensitivity difficulties, night vision problems, double vision, and image ghosting, and other complications such as swelling, thinning, or inflammation of the cornea and infection.


  • 3.

    The KAMRA inlay is a reversible procedure and can be removed; typically, the vision will return to the level prior to the implantation of the inlay.



Indications and Contraindications for KAMRA Inlay Implantation


The indications for the implantation of the KAMRA inlay include phakic or presbyopic patients with general good health and the desire to improve near vision through the mechanism of depth of focus extension. The patients can be between 45 and 60 years of age, who need near visual correction of +1.00 to +2.50 D but do not need glasses or contact lenses for distance vision. The ideal patient should have a cycloplegic spherical equivalent refraction of +0.50 to −0.75 D, with less than 0.75 D of cylinder, less than or equal to 0.50 D in manifest refractive spherical equivalent in the last 12 months prior to the procedure, and with less than 1.00 D difference between the cycloplegic and manifest spherical equivalent refraction.


Some contraindications for the implantation of the KAMRA inlay include severe dry eye, ectasia, keratoconus, residual stromal bed of less of 250 µm, active infection and inflammation of the eye, autoimmune or connective tissue disease, and uncontrolled glaucoma and diabetes. Some medications—such as antihistamines, beta blockers, and birth control pills—can worsen dry eye syndrome, while isotretinoin can change patients’ vision following KAMRA implantation.


KAMRA Inlay Safety and Efficacy


In the pivotal study specifically designed to support FDA approval of the KAMRA inlay, the FDA specified the primary effectiveness criterion as the achievement of uncorrected near visual acuity (UCNVA) of 20/40 or better at 12 months by 75% of the implanted eyes (out of 508 eyes). After the follow-up of the subjects at postoperative 12 months, 24 months, 36 months, and 60 months, whereby 83.5%, 87.2%, 87.1%, and again, 87.1%, respectively, of the subjects had UCNVA of 20/40 or better, they concluded that the KAMRA inlay trial met the efficacy criteria.


The FDA also assessed the safety of the inlay primarily based on three points: (1) changes in corrected distance visual acuity (CDVA), (2) the amount of astigmatism induced in the eyes implanted with the KAMRA inlay, and (3) the occurrence of adverse events in the subjects. The changes in CDVA were evaluated on the basis of two criteria: (1) occurrence of persistent loss of two or more lines of CDVA in less than 5% of the eyes at postoperative 12 months and (2) occurrence of CDVA worse than 20/40 in less than 1% eyes with preoperative 20/20 CDVA at postoperative 12 months. The astigmatism induction evaluation was based on less than 5% of eyes developing astigmatism of greater than 2.00 D from the baseline at 12 months postoperatively. Finally, the adverse events evaluation included occurrence of adverse events related to the inlay in no more than 5% of eyes, with any single adverse event occurring in no more than 1% of eyes. The major reported postoperative events and complications in the FDA pivotal trial are shown in Table 38.3 .



TABLE 38.3

FDA Reported Major Postoperative Adverse Events and Complications (n = 508 eyes)







































Adverse Event At 12 mo (%) At 24 mo (%) At 36 mo (%)
Decrease in CDVA > 2 lines 3.3 5.5 5.9
Inlay removals 3 7.1 8.7
IOP increase > 10 mm Hg above baseline or > 25 mm Hg with clinical findings 3 3.1 3.3
DLK 1.2 1.2 1.2
Conjunctivitis 1 1.4 2
Inlay recentration 0.2 1.2 1.2

CDVA, Corrected distance visual acuity; DLK, diffuse lamellar keratitis; FDA, US Food and Drug Administration; IOP, intraocular pressure.


We did a Pubmed search of all the published articles that reported the safety and efficacy of the KAMRA inlay, using the search words “KAMRA inlay” from the beginning of time until December 5, 2017. We found 10 papers that published the monocular uncorrected near visual acuity (UNVA), binocular UNVA, monocular uncorrected distance visual acuity (UDVA), and binocular UDVA of the KAMRA implanted patients, and calculated the weighted average of the UNVA and UDVA values preoperatively and at postoperative 3, 6, 12, 24, 48, and 60 months where available ( Tables 38.4 through 38.7 ). If we follow the same efficacy criteria as the FDA did, we see that the KAMRA-implanted eyes pass the efficacy criteria of at least 75% of eyes having UNVA of 20/40 or better postoperatively at all follow-up time periods ( Fig. 38.5A ). The implanted eyes achieved a weighted average of 86.9%, 84.9%, 92.5%, 87.6%, 97%, 100%, and 82% at 3, 6, 12, 24, 36, 48, and 60 months, respectively. The weighted average of binocular UNVA is no less than 88% at all follow-up periods ( Fig. 38.5B ). The weighted averages of monocular and binocular UDVA preoperatively and at postoperative 3, 6, 12, 24, 36, 48, and 60 months are shown in Fig. 38.6A, and Fig. 38.6B , respectively. Thus overall, the KAMRA inlay appears to provide significant improvement in UCNVA without significantly impacting the distance visual acuity negatively. A note must be made, however, that AcuFocus has sponsored all currently published studies.



TABLE 38.4

Monocular UNVA for the KAMRA Implanted Eyes
























































































































































































































Monocular UNVA Preoperative
J1 (%) J2 (%) J3 (%) J4 (%) J5 (%) J6 (%)
Study Year Country No. of Eyes Treatment 20/20 20/25 20/30 20/32 20/40 20/50
Moshirfar 2017 USA 508 Comparison of FDA safety and efficacy data between KAMRA and Raindrop
Moshirfar 2016 USA 21 Simultaneous PRK and Inlay 0 0 10 14 14 19
Moshirfar 2016 USA 57 Single site retrospective analysis, presbyopia 0 4 16 28 70
Jalali 2016 Switzerland 50 Presbyopia correction using FLASIK 0 0 2 2 44
Tomita 2015 Japan 21 (Age 40–49) Simultaneous LASIK and KAMRA for hyperopic presbyopia 0 0 0 0 10 19
Tomita 2015 Japan 154 (Age 50–59) Simultaneous LASIK and KAMRA for hyperopic presbyopia 0 0 1 1 1 6
Tomita 2015 Japan 102 (Age 60–65) Simultaneous LASIK and KAMRA for hyperopic presbyopia 0 0 0 1 3 4
Vilupuru 2015 USA 507 Presbyopic patients who underwent contrast sensitivity testing
Dexl 2015 Austria 32 Emmetropic presbyopic eyes 0 0 0 0
Tomita 2013 Japan 223 Presbyopic patients who previously had LASIK
Tomita 2012 Japan 100 Hyperopic (simultaneous LASIK and inlay)
Tomita 2012 Japan 100 Emmetropic (simultaneous LASIK and inlay)
Tomita 2012 Japan 100 Myopic (simultaneous LASIK and inlay)
Yilmaz 2011 Turkey 39 Emmetropic or post LASIK presbyopia 0 0 33
Weighted average 0 4 1.2 3.8 8.3 20.5






























































































































































































































































































































































Monocular UNVA At 3 mo At 6 mo At 12 mo
J1 (%) J2 (%) J3 (%) J4 (%) J5 (%) J6 (%) J1 (%) J2 (%) J3 (%) J4 (%) J5 (%) J6 (%) J1 (%) J2 (%) J3 (%) J4 (%) J5 (%) J6 (%)
Study 20/20 20/25 20/30 20/32 20/40 20/50 20/20 20/25 20/30 20/32 20/40 20/50 20/20 20/25 20/30 20/32 20/40 20/50
Moshirfar
Moshirfar 50 75 75 75 92 100 8 42 42 58 83 100
Moshirfar 12 33 58 77 89 5 28 44 63 82
Jalali 36 80 95 96 98 37 74 86 96 98 37 69 88 93 95
Tomita 57 76 86 100 100 100
Tomita 34 61 71 81 92 97
Tomita 21 43 62 75 90 93
Vilupuru 17 41 66 81 92
Dexl 56 84 86 97
Tomita 37 68 83 92 97 100
Tomita 25 31 69 100
Tomita 57 71 86 100
Tomita 46 61 90 95
Yilmaz
Weighted average 27.6 58.3 89.1 62.6 86.9 94.3 27.6 50.5 80.6 74.2 84.9 95.1 34 60 71.8 80.8 92.5 95.6

FDA, US Food and Drug Administration; LASIK, laser in-situ keratomileusis; PRK, photorefractive keratectomy; UNVA, uncorrected near visual acuity.


TABLE 38.5

Binocular UNVA for the KAMRA Implanted Eyes




























































































































































Binocular UNVA Preoperative
J1 (%) J2 (%) J3 (%) J4 (%) J5 (%) J6 (%)
Study Year Country No. of Eyes Treatment 20/20 20/25 20/32 20/40 20/50
Moshirfar 2016 USA 21 Simultaneous PRK and inlay 0 5 14 14 14 19
Vilupuru 2015 USA 507 Presbyopic patients who underwent contrast sensitivity testing
Dexl 2015 Austria 32 Emmetropic presbyopic eyes 0 2 12 32
Tomita 2015 Japan 21 (Age 40–49) Simultaneous LASIK and KAMRA for hyperopic presbyopia
Tomita 2015 Japan 154 (Age 50–59) Simultaneous LASIK and KAMRA for hyperopic presbyopia
Tomita 2015 Japan 102 (Age 60–65) Simultaneous LASIK and KAMRA for hyperopic presbyopia
Tomita 2013 Japan 223 Presbyopic patients who previously had LASIK
Seyeddain 2013 Austria 24 Emmetropic presbyopic eyes 0 21 44
Yilmaz 2011 Turkey 39 Emmetropic or post LASIK presbyopia 0 28 54
Weighted average 0 8.7 23.1 22.5 37.2 19














































































































































































































































Binocular UNVA At 3 mo At 6 mo At 12 mo
J1 (%) J2 (%) J3 (%) J4 (%) J5 (%) J1 (%) J2 (%) J3 (%) J4 (%) J5 (%) J6 (%) J1 (%) J2 (%) J3 (%) J4 (%) J5 (%) J6 (%)
Study 20/20 20/25 20/30 20/32 20/40 20/20 20/25 20/30 20/32 20/40 20/50 20/20 20/25 20/30 20/32 20/40 20/50
Moshirfar 42 75 92 83 100 8 50 50 58 75 100
Vilupuru 31 61 78 88 98
Dexl 70 90 95 97
Tomita 65 85 94 100 100 100
Tomita 44 71 84 100 100 100
Tomita 32 55 73 85 94 99
Tomita 48 77 90 97 98 100
Seyeddain 17 87 97 36 90 100 21 97 100
Yilmaz
Weighted average 28.7 81.4 92 90.5 100 35.4 66.2 86.6 83.6 90.6 98.6 42.5 70.7 80.7 94.9 97.7 99.6

FDA, US Food and Drug Administration; LASIK, laser in-situ keratomileusis; PRK, photorefractive keratectomy; UNVA, uncorrected near visual acuity.


TABLE 38.6

Monocular UDVA for the KAMRA Implanted Eyes












































































































































































































Monocular UDVA Preoperative
J1 (%) J2 (%) J3 (%) J4 (%) J5 (%) J6 (%)
Study Year Country No. of Eyes Treatment 20/20 20/25 20/30 20/32 20/40 20/50
Moshirfar 2016 USA 57 Single site retrospective analysis, presbyopia 53 68 82 95 96
Jalali 2016 Switzerland 50 Presbyopia correction using FLASIK 14 28 34 77
Vilupuru 2015 USA 507 Presbyopic patients who underwent contrast sensitivity testing
Dexl 2015 Austria 32 Emmetropic presbyopic eyes 100 100 100
Tomita 2015 Japan 21 (Age 40–49) Simultaneous LASIK and KAMRA for hyperopic presbyopia 43 57 76 90
Tomita 2015 Japan 154 (Age 50–59) Simultaneous LASIK and KAMRA for hyperopic presbyopia 40 44 60 75
Tomita 2015 Japan 102 (Age 60–65) Simultaneous LASIK and KAMRA for hyperopic presbyopia 19 27 53 68
Tomita 2013 Japan 223 Presbyopic patients who previously had LASIK
Seyeddain 2013 Austria 24 Emmetropic presbyopic eyes 100 100 100
Tomita 2012 Japan 100 Hyperopic (simultaneous LASIK and inlay)
Tomita 2012 Japan 100 Emmetropic (simultaneous LASIK and inlay)
Tomita 2012 Japan 100 Myopic (simultaneous LASIK and inlay)
Yilmaz 2011 Turkey 39 Emmetropic or post LASIK presbyopia 77 97 100
Weighted average 44.5 53 59.6 69.2 77.2 87.1










































































































































































































































































































































Monocular UDVA At 3 mon At 6 mon At 12 mon
J1 (%) J2 (%) J3 (%) J4 (%) J5 (%) J6 (%) J1 (%) J2 (%) J3 (%) J4 (%) J5 (%) J6 (%) J1 (%) J2 (%) J3 (%) J4 (%) J5 (%)
Study 20/20 20/25 20/30 20/32 20/40 20/50 20/20 20/25 20/30 20/32 20/40 20/50 20/60 20/20 20/25 20/30 20/32 20/40
Moshirfar 49 77 84 89 93 42 65 81 95 96 96
Jalali 57 79 83 98 54 69 74 98 45 74 74 97
Vilupuru 66 82 92 98 99
Dexl 77 85 97
Tomita 86 86 95 100
Tomita 82 88 94 96
Tomita 75 85 93 96
Tomita 78 87 97 100 100
Seyeddain 82 97 97 76 97 100 84 100 100
Tomita 88 94 100 100
Tomita 100 100 100 100
Tomita 78 85 93 93
Yilmaz
Weighted average 58.1 81.4 83.5 97 89 95.3 72.7 84.7 77.7 94.9 98.2 99 96 75.2 85.8 74 94.5 96.4

F-LASIK, Femtosecond–laser in-situ keratomileusis; LASIK, laser in-situ keratomileusis; UDVA, uncorrected distance visual acuity.


TABLE 38.7

Binocular UDVA for the KAMRA Implanted Eyes






































































































Binocular UDVA Preoperative
J1 (%) J2 (%) J4 (%)
Study Year Country No. of Eyes Treatment 20/20 20/25 20/32
Vilupuru 2015 USA 507 Presbyopic patients who underwent contrast sensitivity testing
Dexl 2015 Austria 32 Emmetropic presbyopic eyes 100 100 100
Tomita 2015 Japan 21 (Age 40–49) Simultaneous LASIK and KAMRA for hyperopic presbyopia
Tomita 2015 Japan 154 (Age 50–59) Simultaneous LASIK and KAMRA for hyperopic presbyopia
Tomita 2015 Japan 102 (Age 60–65) Simultaneous LASIK and KAMRA for hyperopic presbyopia
Tomita 2013 Japan 223 Presbyopic patients who previously had LASIK
Yilmaz 2011 Turkey 39 Emmetropic or post LASIK presbyopia 100 100 100
Weighted average 100 100 100












































































































































Binocular UDVA At 6 mo At 12 mo At 24 mo
J1 (%) J2 (%) J4 (%) J5 (%) J6 (%) J1 (%) J2 (%) J4 (%) J5 (%) J1 (%) J2 (%)
Study 20/20 20/25 20/32 20/40 20/50 20/20 20/25 20/32 20/40 20/20 20/25
Vilupuru 48 75 88 98 99
Dexl 100 100 100 100 100
Tomita 100 100 100 100
Tomita 98 98 99 100
Tomita 100 100 100 100
Tomita 100 100 100 100 100
Yilmaz
Weighted average 63.9 82.6 91.7 98.6 99.3 99 99 99.5 100 100 100

LASIK, Laser in-situ keratomileusis; UDVA, uncorrected distance visual acuity.



Fig. 38.5


(A) Weighted average of monocular uncorrected near visual acuity (UNVA) preoperatively and at postoperative 3, 6, 12, 24, 36, 48, and 60 months. (B) Weighted average of binocular UNVA preoperatively and at postoperative 3, 6, 12, 24, 36, 48, and 60 months.





Fig. 38.6


(A) Weighted average of monocular uncorrected distance visual acuity (UDVA) preoperatively and at postoperative 3, 6, 12, 24, 36, 48, and 60 months. (B) Weighted average of binocular UDVA preoperatively and at postoperative 3, 6, 12, 24, 36, 48, and 60 months.




In terms of safety measurement through changes in CDVA postoperatively, following the FDA criteria, the implanted eyes showed good efficacy at all postoperative evaluation except at 60 months ( Fig. 38.7 ). These changes in Snellen lines at various postoperative periods of 3, 6, 12, 24, and 60 months were also found by calculating the weighted averages of changes in Snellen lines reported by 6 published studies on Pubmed ( Table 38.8 ). At 60 months, 18.8% of eyes showed loss of two or more Snellen lines of CDVA. Only one study has been published to date with follow-up of 5 years. At 12 months postoperatively, 11.8% of implanted eyes gained one Snellen line of CDVA and 2.6% of eyes gained two Snellen lines of CDVA.




Fig. 38.7


Weighted average of changes in Snellen lines for corrected distance visual acuity (CDVA) in the KAMRA implanted eyes at postoperative 3, 6, 12, 24, and 60 months.


TABLE 38.8

Changes on Monocular CDVA for the KAMRA Implanted Eyes







































































Changes in Snellen Lines for Monocular CDVA
Study Year Country No. of Eyes Treatment
Moshirfa 2016 USA 57 Single site retrospective analysis, presbyopia
Moshirfar 2017 USA 508 Comparison of FDA safety and efficacy data between KAMRA and Raindrop
Dexl 2015 Austria 32 Emmetropic presbyopic eyes
Tomita 2013 Japan 223 Presbyopic patients who previously had LASIK
Seyeddain 2013 Austria 24 Emmetropic presbyopic eyes
Tomita 2015 Japan 21 (Age 40–49) Simultaneous LASIK and KAMRA for hyperopic presbyopia
Tomita 2015 Japan 154 (Age 50–59) Simultaneous LASIK and KAMRA for hyperopic presbyopia
Tomita 2015 Japan 102 (Age 60–65) Simultaneous LASIK and KAMRA for hyperopic presbyopia
Weighted average

























































































































































































Changes in Snellen Lines for Monocular CDVA
At 3 mo At 6 mo At 12 mo
Study Loss of 2 or More Lines Loss of 1 Line No Change Gain of 1 Line Gain of 2 or More Lines Loss of 2 or More Lines Loss of 1 Line No Change Gain of 1 Line Gain of 2 or More Lines Loss of 2 or More Lines Loss of 1 Line No Change Gain of 1 Line
Moshirfa 0 11 86 4 0 0 18 81 2 0
Moshirfar 1 1
Dexl
Tomita 0 14 78 7 1
Seyeddain
Tomita 0 10 81 5
Tomita 2 8 81 8
Tomita 2 15 62 19
Weighted average 0 11 86 4 0 1 32 159 9 1 5 33 222 32

FDA, US Food and Drug Administration; LASIK, laser in-situ keratomileusis; CDVA, corrected distance visual acuity.


Only one study has been published so far in the literature comparing the stereoacuity before and after KAMRA inlay implantation. Linn et al. report no significant change in stereoacuity; they therefore conclude that the inlay is good for improving near vision in presbyopic patients while preserving distance vision and stereoacuity. In terms of contrast sensitivity, Vilupuru et al. reported no loss of binocular contrast sensitivity in both mesopic and photopic conditions for 507 KAMRA-implanted eyes. In fact, the KAMRA-implanted eyes showed superior contrast sensitivities. Seyeddain et al. reported a statistically significant difference in mesopic and photopic contrast sensitivity measurements in KAMRA-implanted eyes between preoperative and postoperative evaluations. These differences were reported at higher spatial frequencies, however.


Postoperative Complications for KAMRA Inlay


According to the data published by the FDA, risks associated with the KAMRA inlay include visual, ocular, and contrast sensitivity issues already outlined early by KAMRA’s official website, as well as several others. These other risks include the possibility of need for additional time and effort in performing diagnostic tests, such as fundus photography, optical coherence tomography (OCT), binocular indirect ophthalmoscopy, and fluorescein angiography in patients with the KAMRA implanted; the danger of the development of a corneal scar when performing laser photodynamic therapy in implanted eyes; and the possibility of corneal infections, stromal thinning, corneal melting, endothelial cell loss, and inflammation. Yet other FDA report outlined additional risks, including the occurrence of the Pulfrich effect (misperceiving of direction, distances, speed, and location of moving objects due to the difference in the amount of light entering the untreated and the implanted eye), especially during the early postoperative period; chance for intraocular press (IOP) increase owing to postoperative steroid drops; earlier and greater impact of cataract in the implanted eye; and even some permanent vision loss after the inlay explantation.


When simultaneous corneal inlay implantations are done with other refractive procedures, complications can occur. Hoopes et al. reported a case of thermal damage to the KAMRA inlay and closure of the nutritional holes owing to inadvertent touching of the inlay with the neodymium:yttrium aluminum garnet (Nd:YAG) laser beam during posterior capsulotomy. Therefore although the Nd:YAG spots are only temporarily visible, careful consideration must be made regarding laser treatments following inlay implantation. However, several successful reports of simultaneous KAMRA implantation with other refractive procedures, such as photorefractive keratectomy (PRK) and myopic and hyperopic laser in-situ keratomileusis (LASIK), have been published. Similarly, good visual outcomes have been reported for the implantation of KAMRA inlays in eyes that have previously undergone procedures such as cataract surgery, LASIK, pseudophakia, and radial keratotomies. Good visual outcomes have been reported as well for other refractive procedures such as cataract surgery following KAMRA inlay implantation. The effect of simultaneous FS laser–assisted cataract surgery (FLACS) and KAMRA inlay implantation have also been investigated in porcine eyes.


Among the list of postoperative complications reported in the literature for the KAMRA inlay are change in refractive status, infectious keratitis, cataract development, and occurrence of clusters of iron deposits near the Bowman layer. Yilmaz et al. reported four eyes needing explantation out of their study pool of 39 eyes. The reasons for explantation included the occurrence of buttonhole flap, thin flap, and refractive shifts (myopic shift of −2.00 D and hyperopic shift of +3.00 D). Inlay explantation is reported to be safe, with minimal changes in the corneal topography and aberrometry if removed before 6 months. Removal after 6 months may cause permanent changes. Yilmaz et al. also reported five eyes (out of 39 eyes) with cataract development and two eyes with change in refractive status. Cataract progression was to be expected in their study because the mean age of their subjects was 52 years and the authors did a long-term follow-up of 48 months.


Raindrop Inlay


Raindrop near vision inlay is a 2-mm diameter, 32-µm-thick transparent corneal inlay that is made up of approximately 80% water and made using hydrogel similar to soft contact lens ( Figs. 38.8A 38.8B ). The 80% aqueous content of the inlay has a similar refractive index to that of the cornea (1.373); it ensures effective diffusion and transfer of nutrients and oxygen throughout the cornea. The Raindrop inlay is typically placed under a thin FS laser–created flap and allowed to adhere in place. The flap is closed after inlay placement under the flap. Because the inlay works by increasing the curvature of the corneal surface, it should be placed under the flap close to the surface. However, its placement in the corneal pocket has also been studied. A diagram illustrating the principle by which the Raindrop inlay works is shown in Fig. 38.8C . The implantation is done in the nondominant eye to improve near vision, leaving the other eye untouched to achieve good vision at all distances by allowing good coordination between the implanted eye and the untouched eye. The gradient power with smooth transitions for near, intermediate, and distance vision is obtained through reshaping of the Bowman layer and anterior cornea. The reshaped cornea becomes hyperprolate in shape, which helps increase depth of focus. The Raindrop inlay implantation procedure is an outpatient procedure and usually takes just 10 minutes. Healing time is also quite short, allowing most patients to resume their normal activities the following day. The FDA approved the Raindrop inlay in June 2016, making it the second cornea inlay to be approved after the KAMRA inlay.




Fig. 38.8


(A) Raindrop inlay. (B) The Raindrop inlay is less than one-tenth of an inch in size, only 2 mm in diameter, smaller than the eye of a needle. 46 (C) Illustration of the principle of the working mechanism of the Raindrop Inlay. 47






Indications and Contraindications for Raindrop Inlay Implantation


Presbyopic patients desiring improved intermediate and near vision and meeting other criteria who may never have considered eye surgery options can benefit from corneal inlay procedures such as Raindrop. Patients aged between 41 to 65 years needing reading glasses of refractive powers within +1.50 and +2.50 D who do not need glasses for good distance vision and who have not had previous cataract surgery are good candidates for corneal inlays. The manifest refractive spherical equivalent for the ideal patient is between +1.00 D to −0.50 D with refractive cylinder of less than or equal to 0.75 D.


Some contraindications for inlays are the presence of dry eye, aqueous deficiency and meibomian gland diseases, corneal ectasia, keratoconus, certain autoimmune or connective tissue diseases, recent herpes infection, uncontrolled glaucoma or diabetes, active infection or inflammation, and abnormal features on the outer part of the eye.


Raindrop Inlay Safety and Efficacy


Compared to the KAMRA inlay, relatively fewer studies have been published regarding the safety and efficacy of the Raindrop inlay. Three studies in Pubmed that published the monocular UNVA for the Raindrop implanted eyes are shown in Table 38.9 . A study done by Moshirfar et al. (a report submitted to the FDA for the pivotal trial of the KAMRA inlay) made comparisons regarding safety and efficacy between the KAMRA inlay and the Raindrop inlay. Overall, the study reported that the Raindrop inlay met the targeted safety parameter of less than 5% of the study subjects, losing greater than or equal to two lines of CDVA at postoperative 24 months and beyond. After 2 years of implantation, 98% of the patients (total of 373 patients) were able to see with 20/40 vision or better at near distances and 67% were able to see with 20/20 vision or better at near distances. Compared to the efficacy shown by the KAMRA inlay at the same trial, these Raindrop results are actually even better than KAMRA’s, with 28% achieving UNVA of 20/20 or better and 87% achieving UNVA of 20/40 or better at postoperative 24 months.



TABLE 38.9

Monocular UNVA in Eyes with Raindrop Near Vision Inlay Implantation
















































Study Year Country No. of Eyes Follow-Up (mo) J1 (%) J2 (%) J3 (%) J4 (%) J5 (%)
Moshirfar 2017 USA 373 24 67 88 95 98
Verdoorn 2017 Netherlands 16 4 63 79 100
Chayet 2013 Mexico 16 12 51 92 100 100

UNVA, Uncorrected near visual acuity.


Another study comparing the safety and efficacy of the Raindrop inlay with monovision LASIK reported better near and distance visual acuities for the inlay compared to the LASIK procedure. The study reported 60% of inlay patients achieving UNVA of 20/20 or better versus 47% of LASIK patients, and 75% of inlay patients achieving UDVA of 20/32 or better versus 40% of the LASIK patients. In terms of binocular stereopsis, task performance, and patient satisfaction, the inlay group showed better outcomes than the monovision LASIK group, with the inlay group achieving 98 seconds of arc versus the LASIK group achieving 286 seconds of arc for stereopsis, and the inlay group showing patient satisfaction of 79% and 86% versus 66% and 67% for UNVA and UDVA, respectively.


According to the studies conducted by Revision Optics, the Raindrop inlay met the goal of 75% of patients achieving 20/40 or better UNVA at postoperative 24 months by 92% of the subjects achieving the target UNVA and 87% achieving UNVA of 20/25 or better. They also reported refractive stability with a change in manifest refraction spherical equivalent (MRSE) within 1.00 D in at least 98% subjects and a change in MRSE within 0.50 D in at least 88% of the subjects between all consecutive postoperative time points of 0 to 1, 1 to 3, 3 to 6, 6 to 9, 9 to 12, 12 to 18, and 18 to 24 months. ReVision Optics also reported that 98% of patients have been able to read a newspaper or equivalent (20/40 or better at a near distance), 88% of patients have been able to read fine print or equivalent (20/25 or better at a near distance) and 76% of patients have been able to read an onscreen email or equivalent (20/25 or better at an intermediate distance). Studies published in the literature have reported patient satisfaction rates of 82% and 90% in subjects who underwent Raindrop inlay implantation.


Postoperative Complications for Raindrop Inlay


Although it provides some clear benefits, Raindrop inlay implantation has been reported to contribute to glare, halos, foreign body sensation, and pain, with a risk for developing infections, inflammation, new dry-eye syndrome or a worsening of existing dry-eye syndrome, retinal detachment, and a decrease in distance vision. Other complications that may result include corneal swelling, inflammation, thinning, clouding, and melting. ReVision Optics lists several complications that could result from the inlay implantation that include dry eyes, decreased vision, decreased contrast sensitivity, clouding, thinning, scarring, infection, and inflammation of the cornea, increased IOP, and the need for inlay explantation or another eye surgery. The major kinds of adverse events reported by ReVision Optics at postoperative 12, 24, and 36 months are shown in Table 38.10 . Yoo et al. reported the occurrence of glare and loss of some night vision in approximately 40% of patients.


Oct 10, 2019 | Posted by in OPHTHALMOLOGY | Comments Off on Corneal Implants and Inlays
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