Alfonso L. Sabater

Strategies of human corneal endothelial tissue regeneration

Penetrating keratoplasty has previously been the only surgical treatment for patients with corneal endothelial disorders. Recently, posterior lamellar keratoplasty has become a viable and less aggressive alternative technique. However, both transplantation techniques have disadvantages, such as non-immunologic graft failure, allograft endothelial rejection or a global shortage of donor corneas. Over the past few years, several groups have established methods for the isolation, preservation, in vitro cultivation, transplantation, and in vivo stimulation of human corneal endothelial cells in animal models. It is hoped that these new strategies will allow the treatment of more than one patient with one donor cornea, performing autologous corneal endothelium transplantation from a surgical biopsy sample, or stimulating the growth of corneal endothelial cells in vivo. However, several aspects need to be addressed before commencing clinical trials.

Clinical Evaluation of the New Rebound Tonometers Icare PRO and Icare ONE Compared With the Goldmann Tonometer.

Purpose:To compare the participant-obtained intraocular pressures (IOPs) using Icare ONE and the clinician-obtained values using Icare PRO, both rebound tonometers, with Goldmann tonometry (GAT) values and analyze the ease of use of Icare ONE. Methods:One hundred fifty participants were included (60 normal controls, 90 patients with glaucoma/ocular hypertension). The participants measured the IOP 3 times using Icare ONE; a clinician measured the IOP once using Icare PRO. The instruments were used randomly. Clinical data were evaluated to analyze the difficulty of the technique, the effect on the results, and the ease of use of Icare ONE. Results:The mean IOPs with GAT, Icare ONE, and Icare PRO were 16.6±4.43, 17.5±5.42, and 16.6±4.77 mm Hg, respectively. The participant-measured IOP values were within +3 mm Hg of the GAT values in 67.1% of eyes with Icare ONE and in 79.6% with Icare PRO. The limits of agreement were higher with Icare ONE compared with Icare PRO. IOP value errors were found with Icare ONE in eyes with low and high GAT-IOP. The areas under the curve to detect IOPs of 21 mm Hg or higher (GAT) exceeded 0.80 with both tonometers. Young participants reported better ease of use with Icare ONE. No other factors were related to the results. Conclusions:Icare ONE may be useful for patients monitoring their IOP values; most individuals can use the device after a short training session. Icare PRO had better results compared with Icare ONE in all IOP ranges.

Quantification of corneal neovascularization after ex vivo limbal epithelial stem cell therapy

AIMnTo assess cultured limbal epithelial stem cell transplantation in patients with limbal stem cell deficiency by analyzing and quantifying corneal neovascularization.nnnMETHODSnThis retrospective, interventional case series included eight eyes with total limbal stem cell deficiency. Ex vivo limbal epithelial stem cells were cultured on human amniotic membrane using an animal-free culture method. The clinical parameters of limbal stem cell deficiency, impression cytology, and quantification of corneal neovascularization were evaluated before and after cultured limbal stem cell transplantation. The area of corneal neovascularization, vessel caliber (VC), and invasive area (IA) were analyzed before and after stem cell transplantation by image analysis software. Best-corrected visual acuity (BCVA), epithelial transparency, and impression cytology were also measured.nnnRESULTSnOne year after surgery, successful cases showed a reduction (improvement) of all three parameters of corneal neovascularization [neovascular area (NA), VC, IA], while failed cases did not. NA decreased a mean of 32.31% (P=0.035), invasion area 29.37% (P=0.018) and VC 14.29% (P=0.072). BCVA improved in all eyes (mean follow-up, 76±21mo). Epithelial transparency improved significantly from 2.00±0.93 to 0.88±1.25 (P=0.014). Impression cytology showed that three cases failed after limbal epithelial stem cell therapy before 1y of follow-up.nnnCONCLUSIONnThis method of analyzing and monitoring surface vessels is useful for evaluating the epithelial status during follow-up, as successful cases showed a bigger reduction in corneal neovascularization parameters than failed cases. Using this method, successful cases could be differentiated from failed cases.

Amniotic membrane use for management of corneal limbal stem cell deficiency

Purpose of review The current article reviews the most recent surgical techniques for management of corneal limbal stem cell deficiency (LSCD) using amniotic membrane tissue. Recent findings Early successes with amniotic membrane transplantation (AMT) for the treatment of ocular surface disorders have encouraged clinicians to investigate new applications. The use of AMT as a temporary patch in emergency cases in which LSCD may develop has considerably improved the prognosis of these patients. Amniotic membrane does not have stem cells of its own, but it supports regeneration of limbal epithelial stem cells (LESCs). Similarly, the combination of AMT with classic surgical techniques has enhanced the surgical success rates in most case series. Furthermore, based on its advantageous properties as a cell carrier, new applications to support in-vivo and ex-vivo cell expansion have been reported recently. Summary LSCD constitutes a general indication for AMT. Based on the clinical scenario, AMT may be performed alone to support regeneration of LESCs, in combination with other surgical techniques, or even supporting the in-vivo or ex-vivo expansion of LESCs.

Management of retained lens nuclear fragment after cataract surgery

Management of retained lens nuclear fragment after cataract surgery Recently, Pandit et al. published a case of corneal edema resulting from retained lens material 8.5 years after phacoemulsification. We agree with the authors that this complication is more frequent than published reports suggest because we think it could be related to surgical procedures or intraoperative complications in which cortical lens material is left in the periphery of the capsular bag (eg, pupillary miosis). We have seen similar cases, one of them 24 years after cataract surgery. An 11-year-old girl with Marfan syndrome who had extracapsular cataract extraction without intraocular lens implantation in 1981 suddenly developed inferior corneal edema in the right eye and fragments of lens material were found in the anterior chamber (Figure 1). Because she had lost the left eye due to a prior retinal detachment, she refused surgery in the right eye. After 2 months with topical steroids, the lens fragments dissolved completely and the corrected distance visual acuity improved to 20/20. In accord with other authors, we also suggest removal of retained lens fragments to reduce the endothelial damage. However, a conservative approach may be an option in some cases, especially those involving soft lens material. In our case, the endothelial cell count decreased from 2744 cells/mm before the complication to 1624 cells/mm after corneal edema. Endothelial cell count change is related to the duration of the corneal edema and the hardness of the lens material. Endothelial microscopy is recommended in determining the management of these cases. Patients

Combined PI3K/Akt and Smad2 activation promotes corneal endothelial cell proliferation

PurposenThe purpose of this study was to develop a culture method for expansion of corneal endothelial cells (CEC) based on the combined activation of PI3K/Akt and Smad2.nnnMethodsnMorphology, proliferation, and migration of cultured rabbit and nonhuman primate CEC were examined in the presence of the PI3K/Akt activators IGF-1 and heregulin beta in combination with the Smad2 activator activin A. Phenotypic characterization of CEC was performed at the RNA and protein levels. Cell pump function and transepithelial electric resistance were used for in vitro functional assessment of CEC. Finally, ex vivo-expanded rabbit CEC were transplanted into a model of endothelial damage in rabbit corneas.nnnResultsnTreatment of rabbit and nonhuman primate CEC in vitro with IGF-1, heregulin beta, and activin A induced an upregulation of PI3K/Akt and Smad2 signaling pathways and an increase in proliferation and migration of CEC expressing ZO-1, connexin-43, and Na+/K+-ATPase. Cell pump function evaluation revealed the complete functionality of cultured CEC. Injection of rabbit CEC successfully produced recovery of normal corneal thickness in a rabbit model of endothelial dysfunction.nnnConclusionsnWe demonstrated that the combined activation of PI3K/Akt and Smad2 results in in vitro expansion of phenotypic and functional CEC. Expanded cells were able to contribute to restoration of corneal endothelium in a rabbit model. These findings may represent a new therapeutic approach for treating corneal endothelial diseases.

Adjustable centration of subluxated multifocal intraocular lens in upright position

to deliver a sharper, more saturated image for each line. Although this is crucial when scanning though cataracts, both radial and raster scans might miss pathology if it is located between the lines. Radial scans concentrate on the fovea and lose density in more eccentric aspects of the macula. Raster scans provide more even coverage throughout but might miss very focal foveal lesions. In our study, we used the 12-line radial scan exclusively. Many of the patients were scanned on the day of their cataract consultation after they were dilated; however, others were scanned when they returned for biometry. In those cases, dilationwas at the discretion of the technician, who would use it if he or she had difficulty obtaining a good nonmydriatic image.dBetty Rae Klein, MD

Case Report: Explantation of A Binkhorst Iridocapsular Lens >30 Years After Implantation in an Eye With Pseudoexfoliation Syndrome.

AbstractAn 86-year-old man with a Binkhorst 2-loop intraocular lens (IOL) that was implanted in the pupillary sphincter 33 years earlier was examined. The pupil of the implanted eye with the Binkhorst IOL was irregular and the eye had pseudoexfoliation (PEX) syndrome. Pupillary erosion resulted from rubbing of the IOL edge against the pupillary sphincter with PEX material. The IOL was removed because of visual distortion and intense pseudophakodonesis. Gross and light microscopic analyses showed no irido-fibro-lenticular adhesions over the lens or fragments of iris tissue attached to the lens. Scanning electron microscopy showed several pores of different sizes. No inflammatory cells were present, suggesting that the IOL was well tolerated.The case suggested that the pupillary ruff was not a good location for implantation of an IOL in an eye with PEX. Caution is recommended before implanting or suturing an IOL close to the pupillary border in eyes with PEX during cataract surgery.

Surgical pearl: capsular tension ring insertion technique.

behind the iris and into the anterior chamber (see Figure 1 in our case report). The fragment then returned to its retro-iris position. Twenty minutes of head positioning was required in the operating room to bring the nuclear fragment back into the anterior chamber. Once it was visible, sodium hyaluronate was used to stabilize the large nuclear fragment, which was then removed with phacoemulsification. At the heart of our cases lies the unexpected presentation of acute corneal edema and the question of how the lens fragment remained sequestered for such a prolonged period of time. We initially suspected a retained nuclear fragment but also entertained a diagnosis of viral endotheliitis or iritis when we could not identify a retained lens fragment. Oliveira et al. reported retained nuclear fragments after an iris elevation was observed in otherwise normal pseudophakic eyes. No signs or symptomswere present. The authors hypothesized that the posterior iris location of the nuclear fragment may have resulted in the absence of an inflammatory reaction or other findings. In our case, it is unclear whether the nuclear fragment remained sequestered in its posterior iris location or whether it intermittently moved into the anterior chamber, almost 1 year after cataract surgery. These unusual cases highlight the potential difficulty and importance of identifying retained nuclear fragments immediately after cataract surgery and years later. However, when a nuclear fragment is identified, even in an asymptomatic individual, we believe that the fragment should be removed because of the unpredictable onset of complications. dStephen C. Kaufman, MD, PhD, Ali Mokhtarzadeh, MD, Dara D. Koozekanani, MD, PhD, Alessandro Meduri, MD, PhD