490 likes | 565 Vues
Refractive Surgery Techniques and Technology 101. Clay Falknor, M.D. Presbyterian Hospital of Dallas August 9, 2005. Case Example.
E N D
Refractive Surgery Techniques and Technology 101 Clay Falknor, M.D. Presbyterian Hospital of Dallas August 9, 2005
Case Example A 26 yo CM fourth-year medical student presents with best corrected vision of –4.50 OD and –5.00 OS, now with c/o wanting to get rid of his contacts, and wanting to see the alarm clock in the morning so he won’t be late for rounds. He presents to a cornea fellow at a certain prestigious medical school for refractive surgery consultation holding a discount coupon he got by email.
Basics of Optics [1] [1]
Basics of Optics P = Power np = nodal point f,f’ = primary and secondary focal points n,n’ = refractive indices [1] Refraction is measured in diopters (D) = reciprocal of focal length in meters
Refractive media of eye • Transparent media [2]
Accommodation • Amplitude of accommodation is the number of diopters the eye can accommodate • Accomplished by the variable optical power of the crystalline lens [3]
Vision Correction Basics • Far point: the point at which an object must be placed along the visual axis for light rays to be focused on the retina when the eye is not accommodating. • Near point: the point at which an object will be in focus on the retina when the eye is fully accommodating. Any object closer than the near point will not be in focus.
Emmetropia • The far point for the emmetropic eye is at infinity. • Nearer objects brought into focus on retina with accommodative power of the lens. [4]
Myopia (Near-sightedness) • The far point for the myopic eye is between the cornea and infinity • Refractive myopia: too much refractive power due to steep corneal curvature or high lens power • Axial myopia: elongated globe (each 1mm axial elongation = 3D myopia) • Overall, the cornea and lens are too “strong” for the length of the globe. • Distant objects unclear, but near objects within focal point of the eye seen clearly. • Correct with minus lens [4]
Hyperopia (Far-sightedness) • The far point for the hyperopic eye is beyond infinity • The cornea and lens are too “weak” for the length of the globe. • Distant objects focused on the retina with accommodation, but clear near vision is difficult) • Correct with plus lens [4]
Astigmatism • Very common, up to 95% of eyes w/ detectable astigmatism, and 10-20% >1D. • Can be naturally occurring or surgically induced. • Most often caused by a toric cornea, and less commonly by astigmatic effects of the lens • Refractive power of the eye different in various meridians. Light can never be brought into focus on a single point regardless of distance. • May occur with either myopia or hyperopia. • Regular astigmatism termed “with the rule” when steepest corneal meridian close to 90°, and “against the rule” when close to 180°. • When astigmatism regular but not close to 90° or 180°, termed oblique. [1]
Astigmatism [1]
Astigmatism • Astigmatism creates two focal lines, one closer to the cornea formed by the more powerful corneal meridian, and the second further from the cornea formed by the less powerful meridian. • The Circle of Least Confusion is the smallest cross-sectional area between the two focal lines, a circular cross-section of the conoid of Sturm. • The goal of refractive correction is to place the circle of least confusion on the retina. [4] [1]
Presbyopia • As the crystalline lens hardens with age, it is no longer able to attain the more spherical form, leading to decreased accommodation. • Net Effect: A lessening of the accommodative amplitude and a increase in the near point of the eye. • Usually has onset in 5th or 6th decade. • Presbyopia is not correctable with laser surgery, and in fact, the surgery may hasten its noticeable development • Solution: Reading glasses
More vision correction basics • A lens with the focal point coincident with the far point of the eye allows parallel light rays from infinity to be focused on the retina
Spectacles and Contact Lenses • Correct both sphere and cylindrical refractive errors. • Prescription read as spherical error, then cylindrical error, then axis of astigmatism. • Myopia treated with concave lenses with minus power (divergent) to focus light on the retina. • Hyperopia treated with convex lenses with plus power (convergent). • Astigmatism corrected with cylindrical lenses. • Ex. of myopic Rx w/ astigmatism: -3.50 + 1.50 x 090 • Ex. of hyperopic Rx w/ astigmatism: +4.00 – 2.00 x 180 [1]
Spectacles and Contact Lenses • Aberrations induced by thick lenses • Spherical aberration: light at periphery of lens refracted more than at center, causing night myopia due to larger pupil at night. • Coma: A comet-shaped blur when object and image are off the optical axis. • Astigmatism of oblique incidence: When a spherical lens is tilted, it gains a small astigmatic effect causing curvature of the field. Helpful since matches curvature of the retina. • Chromatic aberration: Shorter wavelengths bent more. • Distortion: Greater magnification in periphery. A high plus lens produces pincushion effects, and high minus produces barrel distortion. [1]
Refractive Surgery Techniques • Radial Keratotomy (RK) • Freeze keratomileusis • Photorefractive Keratectomy (PRK) • Laser Epithelial Keratomileusis (LASEK) • Laser-assisted in-situ Keratomileusis (LASIK) • Others: • Astigmatic Keratotomy (AK) • Intracorneal ring segments (Intacs) • Phakic Intraocular Lens Implants • Refractive lensectomy
Radial Keratotomy • First used in U.S in 1978. • Treats low to mod myopia in outpt setting using topical anesthetics. • RK reduces myopia by steepening the cornea peripherally, which secondarily flattens the cornea centrally. • The surgeon makes deep radial incisions with a diamond blade in a spoke-like pattern, leaving a clear optical zone in the center. • Refractive effect determined by the number, length, and depth of the incisions, as well as the size of the spared central optical zone. • The smaller the optical zone, the greater the central corneal flattening (reduction in myopia), but greater risk of side-effects. [5]
RK • 8 incision RK shown above with uniform central optical zone • American (centrifugal with angled blade), Russian (centripetal with vertical blade), and combined techniques • Russian technique allows for deeper incisions and more refractive effect, but greater risk of entering optical zone. • Standardized nomograms based on analysis of previous cases determine the number of incisions and size of optical zone to create a given refractive effect. Typically 4 incisions for low myopia, 8 for moderate. [6]
RK • Infected RK incision shown above left • 16 incision RK w/ hypertrophic scarring & irregular optical zone above right • Advantage: RK patients have excellent uncorrected vision on POD1. • Disadvantage: As with other surgical procedures, incisions leave permanent changes to the cornea, as contrasted with contact lenses or spectacles. The cornea may be left weakened. • Complications include: glare, diurnal fluctuation in refraction, hyperopic shift, corneal perforation, infection. [1] [6]
RK Evidence • Prospective Evaluation of Radial Keratotomy (PERK) • 60% of RK treated eyes were w/in 1D of emmetropia up to 10 years post-op. • After 10 years, 53% at least 20/20 uncorrected, and 85% at least 20/40. • 43% eyes w/ progressive shift toward hyperopia ≥ 1D after 10 years, and worse for eyes w/ optical zone <3mm diam. • Only 3% pts lost 2 or more lines of best corrected acuity, and all 20/30 or better best-corrected. • <1% c/o severe glare or starburst during night. • 2% with corneal perforation, none req’d suturing. • Best results for low myopia group (-2.00 to -3.00D) [1]
Laser technology • Excimer laser: EXCited dIMER • AKA “cool laser beam” because little thermal damage to adjacent tissues. • 193nm wavelength ultraviolet laser with sufficient energy to disrupt intermolecular bonds within the corneal stromal tissue (photoablative decomposition). • First excimer lasers FDA approved in 1995, with beam width 4-5mm, now available less than 100 microns. • Each laser pulse removes a given volume of stroma • Three types of laser application: wide-area ablation, scanning slit, and flying spot lasers. [1,4,5]
Laser technology • In myopia, laser flattens central cornea to decrease its focusing power to bring secondary focal point back to retina. • In hyperopia, the laser removes peripheral corneal tissue thereby secondarily steepening the central cornea, increasing the focusing power of the cornea. • Astigmatism treated with elliptical or cylindrical beams that flatten the steepest corneal meridian. • To minimize glare and halos, optical zone should be larger than the dilated pupil.
Corneal Topography • Computer-based videokeratography used to evaluate the corneal curvature. Most systems use a video camera to detect reflected images of rings projected onto the cornea, while others use slit beams, which can also measure the corneal thickness. • Pre-operative and post-operative topographic maps can be used to generate a “difference map” to isolate the procedure-induced changes. • Subtle abnormalities, such as early keratoconus or contact lens-induced corneal warping can be picked up. [1]
Photorefractive Keratectomy • PRK can effectively treat low to mod myopia or hyperopia +/- astigmatism. • Performed as outpt with topical anesthesia. • First, the corneal epithelium in the area to be ablated is removed to expose Bowman’s layer and the underlying corneal stroma (spatula, laser). • Excimer laser then applied as directed by the corneal topography-driven computer program. • Topical antibiotics, steroids, and NSAIDs applied, along with a bandage contact lens (BCTL) [5]
PRK • In the post-op period, pt may experience tearing, photophobia, blurred vision, and discomfort due to abrasion of central epithelium. • This can be controlled with topical steroids and NSAIDs. • Pts occ. require systemic analgesia for severe pain • BCTL removed once epithelial defect healed (avg 3-4 days). • Abx continued several more days, and steroids for up to 3 months post-op. • Visual acuity improves once the epithelial defect heals, but fluctuates for a few months and finally stabilizes at ~3 months. • Glare, halos, and dry eye symptoms common the first month post-op, usually diminishing/disappearing by 3-6 months. [4,5]
PRK [6] [1] [5] • Left: mild stromal haze at 3 months • Center: moderate-to-severe stromal haze at 6 months • Right: light microscope of rabbit cornea showing epithelial hyperplasia in ablated region • Bottom: fluorescent microscope in rabbit cornea 1 month post PRK showing new connective tissue deposition between stained old stroma and epithelium. • Post-op corneal haze seen in a minority of patients at 3 months, and in none at 1 year • Initially following PRK, corneal epithelium hyperplastic, modifying refraction. • Deposition of new collagen and GAGs by activated stromal keratocytes, manifesting as stromal haze or subepithelial scarring. [5]
PRK Evidence • A 2001 prospective study of 72 cases showed with significance that a larger ablation area (7mm) with transitional zones has less pronounced corneal optical aberration after PRK than with first generation (5mm) ablation areas with out transitional zones. [7] • A 1999 multi-center prospective study demonstrated PRK to correct myopia from -1 to -10D +/- astigmatism showed refractive stability, excellent UCVA with no significant loss of BSCVA, and very low levels of corneal haze at one year post-op. [8] • A 2004 British 12-year prospective follow-up study of PRK patients showed that for mild myopia, refractive stability achieved at 1 year was maintained to 12 years without hyperopic shift, diurnal fluctuation, or late regression in the long term. Night halos remained a significant problem in the subset of pt’s with small ablation zones. [9]
PRK Evidence • A large 1998 prospective study (3000 cases) in Spain to monitor complications of PRK for myopia +/- astigmatism at two years revealed that only 0.7% of eyes lost 2 or more Snellen lines for BCVA at one year post-op. Retreatment for undercorrection was performed in 7% of the low myopia group and 39% of the high myopia group. There were no cases of progressive hyperopia. Severe corneal haze was only present in 0.5% at one year. Only rare occurrences of surgically induced astigmatism (0.5%), delayed re-epithelialization, or recurrent corneal erosion. [10] • Results of PRK are comparable to RK for similar magnitudes of myopia. • 68% w/in 1D of emmetropia uncorrected (RK 60%) • 60% with at least 20/20 uncorrected (RK 53%) • 90% with at least 20/40 uncorrected (RK 85%) • For low to mod myopia (-1.5 to -3.0D), 80% ≥ 20/20 uncorrected • Hyperopic shift infrequent in PRK compared to RK.
Keratomileusis [5]
Laser Sub-Epithelial Keratomileusis • LASEK can treat mild to moderate myopia and hyperopia +/- astigmatism. • Can be performed as an outpt with topical anesthesia • The corneal epithelium is incompletely incised using a microkeratome with a 70 micron deep blade. • A hinge is left at the 12 o’clock position. • Dilute alcohol (20%) drops are applied to the exposed tissue and left for ~30 seconds. The area is then washed with water and allowed to dry. The excimer laser is applied as in PRK to the sub-epithelial stroma. • The epithelial flap is repositioned afterward. [4,5]
LASEK Evidence • In theory, since the flap is repositioned with the epithelium intact, there is less post-op pain, faster visual recovery, and less incidence of infection. • A 2004 randomized prospective clinical trial at Travis Air Force base compared LASEK with PRK in different eyes in the same patients (n=30) for subj. pain levels, visual acuity, and corneal healing. • No statistical advantages in pain levels or in visual acuity. • There was a statistically significant smaller median epithelial defect in the LASEK-treated eyes on POD1, but by POD3 the PRK defects were smaller and by POD7, there were no detectable defects in either group. • Overall, no clinical advantage was seen in LASEK over PRK. [11]
LASEK Evidence • A 2002 non-randomized, retrospective study of 58 LASEK-treated eyes with myopia +/- astigmatism resulted in 45% with 20/40 or better UCVA at POD1, and 89% at 1 month, and 97% at 6 months, with 73% with UCVA 20/20 or better. 7% of eyes had visually significant corneal haze at 6 months, and no eyes lost 2 or more lines of BSCVA. [12] • Similar results found in a 2002 South Korean study with 6 month follow-up of LASEK treated eyes for low to moderate myopia (-3.25 to -7.00D). [13]
Laser-assisted in-situ Keratomileusis • LASIK can treat mild, moderate, and high myopia and hyperopia +/- astigmatism. • Can also be performed as an outpt with topical anesthesia • LASIK is now the most commonly performed refractive surgery in the world. • A suction ring is applied to the anesthetized cornea and a microkeratome is used to raise a corneal flap of ~160microns thickness (25-30% of the corneal thickness), hinged at the 12 o’clock position. • The suction is turned off and the flap is lifted aside, exposing stromal tissue • The excimer laser is applied as with PRK and LASEK, controlled by the topography-driven computer software, to reshape the cornea. • The flap is replaced on the stromal bed without sutures or a BCTL, as the endothelial pumps create a driving force to keep the flap in position. [5]
LASIK • The use of the suction ring helps hold the cornea steady and provides for a uniform cut by the microkeratome. • Flaps can be formed by an automated process involving a blade guide on the suction ring to guide a turbine-driven microkeratome, producing a very smooth, regular cut • Patients usually sent home on topical antibiotics, steroids, and NSAID drops. Pt is usually seen ~POD 1, and 7, then at 1, 3 and 6 months. • Benefits include little pain, quick recovery of vision, and potential to treat higher levels of myopia. LASIK enhancements are also easily performed. [1]
A 1996 Saudi Arabian retrospective study looked at the efficacy of LASIK to correct myopia from -2 to -20D, and showed promising results in the entire range of refractive error. [14] A 2001 cohort study by McDonald et al also showed refractive efficacy and stability, good UCVA outcomes, no significant loss of BCVA, and accurate correction of astigmatism in the range of -1 to -11D with up to -5D of astigmatism. [15] At six months, for spherical myopes, UCVA 20/20 or better in 61% 20/40 or better UCVA in 94% 0.6% lost 2 lines of BSCVA, and none > 2 lines At six months for astigmatic myopes, UCVA 20/20 or better in 52% 20/40 or better UCVA in 94% 0.9% lost 2 lines of BSCVA, and none > 2 lines A refractive stability was achieved between 1 and 3 months in 98% of spherical and 99% of astigmatic myopes, and 100% between 3-6 months for both groups. LASIK Evidence
LASIK Evidence • A 2001 retrospective study by Tabbara et al showed efficacy in LASIK refractive correction of hyperopia from +0.5 to +11.5D at six months follow-up [16]: • 44% with UCVA of 20/20 or better • 98% with UCVA of 20/40 or better
LASIK Evidence • Even though simultaneous bilateral LASIK has been shown to be safe (Gimbel et al, 1999 [17]), Chiang et al in 1999 showed that the refractive predictability between a person’s two eyes after LASIK is correlated, and therefore that using a correction gained from the first eye to customize the procedure for the second eye has better outcomes, esp. in mild myopes. [18] • A prospective 2001 study at Bascom Palmer and a retrospective study at Univ. of Washington showed that irritation, or “dry eye” symptoms are due to sensory denervation of the ocular surface following bilateral LASIK (neurotrophic epitheliopathy), and resolve by 6 months post-op. [19], [20] • A 2003 Ohio State retrospective study examined risk factors for decreased patient satisfaction and showed that most are satisfied with their vision after LASIK, but that increasing age, flatter pre-operative minimum corneal curvature, and surgical enhancement were significant factors for decreased satisfaction and increased night vision symptoms. [21]
Comparisons • PRK vs. LASIK • 1998 prospective study Hersh et al) [22] showed similar refractive outcomes, though faster results in LASIK, and undercorrection more likely in LASIK than PRK • 2000 control-matched study also showed equal refractive outcomes between LASIK and PRK up to -9D, but LASIK 2x more likely to cause halos [23]. • 1999 El-Maghraby et al showed LASIK significantly lowers post-operative pain and hastened recovery of vision, but did not alter refractive outcomes [24]. • LASEK vs. LASIK • LASEK with thinner flap, corneal ectasia less likely • LASIK needs more complicated equipment with higher risk of intraoperative flap complications. • LASEK lowers risk of DLK • Lost LASEK flap less risky than a lost LASIK flap. • LASEK can cause stromal haze similar to PRK • More studies needed
Wavefront-guided LASIK • Wavefront testing allows for the measurement of not only myopia, hyperopia, and regular astigmatism, but also higher-order aberrations (irregular astigmatism). • A beam of light is shone onto the eye, reflected off the back of the eye and refracted on its way back out. The light then enters a micro-lens array to produce a spot image array of reflected light. • Computer analysis determines the relative displacement of each spot image. The images are then processed to give the local slope and character of the wavefront light. • A 2004 Israeli prospective, non-randomized comparative clinical study showed that WFG LASIK patients have significantly improved contrast sensitivity compared to the standard LASIK patients at one month post-op, even though visual acuities were not different with significance between the groups. [25]
LASIK Complications • Potential complications: • Intra-operative flap complications: A 2000 UCLA retrospective study of ~4000 eyes found a microkeratome complication rate of 0.7%, but a higher rate with surgeon inexperience (1.3% in surgeons first 1000 eyes). [26] • Post-operative flap complications • Flap-bed interface epithelialization: Walker et al in 2000 showed that epithelial growth at the interface could significantly be reduced by irrigating the stromal surfaces and using a BCTL for one day. [27] • Irregular astigmatism • Infection: • Diffuse lamellar keratitis (DLK): (AKA Sands of Sahara syndrome) Wavy inflammatory reaction at LASIK flap interface 1-3 days post-op of unknown cause. Treatment involved high-dose topical steroids or lifting the flap to irrigating the interface. • Progressive corneal ectasia: progressive corneal thinning and steepening with worsening irreg. astigmatism thought to result from too thin a stromal bed after LASIK. Most believe stromal bed thickness should be at least 250 microns.
LASIK Complications • A 1998 Canadian retrospective study showed that even with early techniques, there was no significant loss of BCVA. 1.9% of procedures involved microkeratome-related complications, and 1.3% involved complications with the suctioning device. Only 1.8% involved post-op complications requiring repositioning of shifted or wrinkled flaps. [28]
Poor LASIK Candidates • Thin cornea • Irregular astigmatism • Keratoconus • Anterior basement membrane dystrophy • Herpes keratitis • Unstable refraction • Pregnant or nursing (unstable refraction) • History of dry eyes [1]
Good LASIK Candidates • Proper expectation of outcome • >18 years old • Stable refraction for at least 1 year (<1D change) • Sufficient corneal thickness • Good wound healing potential (no immunosuppresing conditions or medications or autoimmune conditions). • Mild to moderate refractive error (though high myopes and hyperopes, as well as higher-order aberrant eyes are relatively good candidates) [5]
Other options… • Astigmatic keratotomy (AK) • Phakic intraocular lens implants • Refractive lensectomy • Intracorneal rings [6] [1]
Sources Cited • 1) Vander, James F. and Janice A Gault, Ophthalmology Secrets, 2nd ed. 2002, pp 11-129. • 2) Netter, Frank H. Atlas of Human Anatomy, 2nd ed. 2001, pg 82. • 3)Rohen, Johannes W., Chihiro Yokocki and Elke Lutjen-Drecoll Color Atlas of Anatomy 4th ed. 1998, pg 129. • 4) Weichel, Eric D and Kraig S Bower, “Laser Refractive Surgery,” www.UpToDate.com, 2005. • 5)Abad, Juan Carlos, and Dimitri Azar, Yanoff: Ophthalmology, 2nd ed. 2004. Chapter 15. • 6)Friedman, Neil J., Roberto Pineda II, and Peter Kaiser, The Massachusetts Eye and Ear Infirmary Illustrated Manuel of Ophthalmology, 1998. • 7)Endl, MJ, et al “Effect of larger ablation zone and transition zone on corneal optical aberrations after photorefractive keratectomy” Arch Ophthalmol 2001, Aug; 119(8):1159-64. • 8)McDonald, MB, et al “Photorefractive keratectomy for low-to-moderate myopia and astigmatism with a small-beam, tracker-directed excimer laser.” Ophthalmology 1999, Aug; 106(8):1481-8. • 9)Rajan, MS, et al “A long-term study of photorefractive keratectomy; 12-year follow-up.” Ophthalmology 2004, Oct; 111(10):1813-24. • 10)Alio, JL, et al “Complications of photorefractive keratectomy for myopia: two year follow-up of 3000 cases” Cataract Refract Surg 1998, May; 24(5):619-26. • 11)Pirouzian, A, et al “A randomized prospective clinical trial comparing laser subepithelial Keratomileusis and photorefractive keratectomy” Arch Ophthalmol 2004, Jan; 122(1):11-6. • 12)Rouweyha, RM, et al “Laser epithelial keratomileusis for myopia with the autonomous laser” J Refract Surg 2002, May-Jun; 18(3):217-24. • 13)Lee, JB, et al “Laser subepithelial keratomileusis for low to moderate myopia: 6-month follow-up” J Ophthalmol 2002, May-Jun; 46(3)299-304. • 14)Zadok, D, et al “Hyperopic laser in situ keratomileusis with the Nidek EC-5000 excimer laser” Ophthalmology 2000, Jun; 107(6):1132-7. • 15)McDonald, MB, et al “Laser in situ keratmileusis for myopia up to -11 diopters with up to -5 diopters of astigmatism with the summit autonomous LADARVision excimer laser system” Ophthalmology 2001, Feb; 108(2):309-16.
Sources Cited Continued • 16)Tabbara, KF, et al “Laser in situ keratomileusis for the correction of hyperopia from +0.50 to +11.50 diopters wit the Keracor 117C laser” J Refract Surg 2001, Mar-Apr; 17(2):123-8. • 17)Gimbel, HV, et al “Simultaneous bilateral laser in situ keratomileusis: safety and efficacy” Ophthalmology 1999, Aug; 106(8):1461-7. • 18)Chiang, PK, et al “Comparing predictability between eyes after bilateral laser in situ keratomileusis: a theoretical analysis of simultaneous versus sequential procedures” Ophthalmology 1999, Sep; 106(9):1684-91. • 19)Battat, L, et al “Effects of laser in situ keratomileusis on tear production, clearance, and the ocular surface” Ophthalmology 2001, Jul; 108(7):1230-5. • 20)Wilson, SE “Laser in situ keratomileusis-induced (presumed) neurotrophic epitheliopathy” Ophthalmology 2001, Jun; 108(6):1082-7. • 21)Bailey, MD, et al “Patient satisfaction and visual symptoms after laser in situ keratomileusis” Ophthalmology 2003, Jul: 110(7):1371-8. • 22)Hersh, PS, et al “Photorefractive keratectomy versus laser in situ keratomileusis for moderate to high myopia. A randomized prospective study” Ophthalmology 1998, Aug; 105(8):1512-22. • 23)Pop, M, et al”Photorefractive keratectomy versus laser in situ keratomileusis: a control-matched study” Ophthalmology 2000, Feb; 107(2):251-7. • 24)El-Maghraby, A, et al “Randomized bilateral comparison of excimer laser in situ keratomileusis and photorefractive keratectomy for 2.50 to 8.00 diopters of myopia” Ophthalmology 1999, Mar; 106(3):447-57. • 25)Kaiserman, I, et al “Contrast sensitivity after wave front-guided LASIK” Ophthalmology 2004, Mar; 111(3):454-7. • 26)Tham, VM, et al “Microkeratome complications of laser in situ keratomileusis” Ophthalmology 2000, May; 107(5):920-4. • 27)Walker, MB, et al “Incidence and prevention of epithelial growth within the interface after laser in situ keratomileusis” Cornea 2000, Mar; 19(2):170-3. • 28)Gimbel, HV, et al “Incidence and management of intraoperative and early postoperative complications in 1000 consecutive laser in situ keratomileusis cases” Ophthalmology 1998, Oct; 105(10):1839-47.