Concomitant chemotherapy and radiation for the treatment of advanced-stage endometrial cancer.

INTRODUCTION: Ccombination chemotherapy and radiation therapy is used for adjuvant treatment of stage III-IV endometrial cancer. The goal of this study was to review the treatment duration, toxicity, and survival for patients treated with concomitant chemotherapy and radiation. METHODS: Women with stage III-IV endometrial cancer treated with concurrent chemotherapy and radiation between 2006 and 2013 were included. Toxicities were classified per CTCAE v3.0 and RTOG/EORTC late radiation morbidity scoring. Descriptive statistics were used to quantify treatment and toxicities. Kaplan-Meier method was used to estimate survival. RESULTS: Fifty-one patients met our inclusion criteria. Median age was 60 (range 33-85). Thirty-six patients (70.6%) had endometrioid histology, 13 patients (25.5%) had serous, clear cell, or mixed histology, and 2 women (3.9%) had carcinosarcoma. Forty-eight patients had stage III disease and three patients were stage IVB. Mean treatment duration was 107 ± 19 days. Forty-two patients received all planned chemotherapy, and 16 patients required a dose reduction. Thirty-four patients (66.7%) experienced grade 3-4 toxicities, the majority of which were hematologic. There were no deaths related to therapy. Eighty-six percent of patients received leukocyte growth factors, and 25% of patients received a blood transfusion. Seven late grade 3-4 complications occurred: four gastrointestinal and two genitourinary, and one patient had ongoing neuropathy. Median progression-free survival was 42.8 months (range 4.4-81.5 months) and median overall survival was 44.9 months (range 5.1-82.6 months). Three-year overall survival was 80%. CONCLUSION: Concomitant chemotherapy and radiation is an adequately tolerated treatment modality that allows for shorter treatment duration.

A new surgical technique for deep stromal, anterior lamellar keratoplasty.

AIMS: To describe a new surgical technique for deep stromal anterior lamellar keratoplasty. METHODS: In eye bank eyes and sighted human eyes, aqueous was exchanged by air, to visualise the posterior corneal surface--that is, the "air to endothelium" interface. Through a 5.0 mm scleral incision, a deep stromal pocket was created across the cornea, using the air to endothelium interface as a reference plane for dissection depth. The pocket was filled with viscoelastic, and an anterior corneal lamella was excised. A full thickness donor button was sutured into the recipient bed after stripping its Descemet's membrane. RESULTS: In 25 consecutive human eye bank eyes, a 12% microperforation rate was found. Corneal dissection depth averaged 95.4% (SD 2.7%). Six patient eyes had uneventful surgeries; in a seventh eye, perforation of the lamellar bed occurred. All transplants cleared. Central pachymetry ranged from 0.62 to 0.73 mm. CONCLUSION: With this technique a deep stromal anterior lamellar keratoplasty can be performed with the donor to recipient interface just anterior to the posterior corneal surface. The technique has the advantage that the dissection can be completed in the event of inadvertent microperforation, or that the procedure can be aborted to perform a planned penetrating keratoplasty.

Posterior lamellar keratoplasty for a case of pseudophakic bullous keratopathy.

PURPOSE: To describe a new surgical technique for posterior corneal transplantation. METHODS: An elderly patient had painful, pseudophakic bullous keratopathy with low visual potential. Through a 9.0-mm scleral tunnel incision, a midstromal pocket was dissected across the cornea, and a posterior lamellar disk 7.0-mm in diameter, which consisted of posterior stroma, Descemet membrane, and endothelium, was excised. A similarly shaped donor posterior disk was implanted in the recipient opening without suture fixation, and the scleral incision was sutured. RESULTS: Throughout the postoperative period, the posterior corneal transplant remained clear and in position. Three months after surgery, the "suture-in" astigmatic error was 3.5 diopters. Pachymetry measured 0.44 mm. CONCLUSION: Posterior lamellar keratoplasty may be a new surgical approach with which to manage corneal endothelial disorders.

A technique to visualize corneal incision and lamellar dissection depth during surgery.

PURPOSE: To describe a surgical technique to visualize the depth of corneal incisions and lamellar stromal dissections during surgery. METHODS: In porcine cadaver eyes, the aqueous was exchanged by air. Thus an air-to-endothelium interface (i.e., a useful optical surface) was created at the posterior corneal surface. The air-to-endothelium interface was used as a reference plane to visualize the corneal thickness and the relative depth of corneal incisions and dissections. Freehand peripheral corneal incisions, tangential keratotomy incisions, and lamellar stromal dissections were made at an intended corneal depth of 60, 80, and 99%. Light microscopy was used to measure the relative depth of the incisions and dissections. RESULTS: Achieved depth for peripheral corneal incisions averaged 65.2+/-5.3%, 78.8+/-5.1%, and 93.4+/-6.0%, respectively (p<0.05); and for tangential keratotomy incisions, 68.2+/-7.3%, 83.2+/-4.4%, and 95.8+/-3.6%, respectively (p<0.05). Achieved depth for lamellar stromal dissections averaged 58.3+/-9.4%, 81.1+/-3.4%, and 94.4+/-1.5%, respectively (p<0.05). Microperforations occurred with three incisions made at 99% intended depth. CONCLUSION: During surgery, the depth of incisions and lamellar dissections relative to the corneal thickness can be visualized by filling the anterior chamber with air (i.e., by creating an optical interface at the posterior corneal surface).

A surgical technique for posterior lamellar keratoplasty.

PURPOSE: To design a surgical technique for transplantation of posterior corneal tissue, while leaving the recipient anterior cornea intact. METHODS: In human cadaver eyes, and in a cat and monkey model, recipient eyes had an 8.0-mm limbal incision made with a diamond blade set to 50% of central pachymetry. A stromal pocket was created across the cornea, and a 6.0-mm diameter posterior lamellar disc was excised. A donor posterior disc was implanted into the recipient opening, and the limbal incision was sutured. The procedure was evaluated with keratometry, biomicroscopy, endothelial (supra)vital staining, and light microscopy. RESULTS: In human cadaver eyes, post-operative astigmatism averaged 1.2 D (SD, +/- 0.6 D). Posterior transplants showed an intact endothelial cell layer with 1.0% (SD, +/- 1.2%) of cell death. In the animals, six (75%) eyes had clear transplants 2 weeks after surgery; one of these eyes later developed an allograft rejection. Two (25%) eyes showed corneal decompensation, because of inverted implantation of the donor disc. Microscopy showed minimal scarring at the donor-to-host interface and a normal wound-healing response at the posterior stromal wound edges. CONCLUSION: In experimental models, posterior lamellar keratoplasty can be performed through a limbal incision and a mid-stromal pocket. The procedure may be a potential alternative in the surgical management of corneal endothelial disorders.

Bilateral, anterior stromal ring opacity of the cornea.

AIMS/BACKGROUND: To describe a bilateral, mid peripheral, ring-shaped corneal opacity, not resembling any known corneal degeneration, dystrophy, or other disorder, and occurring without ocular or systemic disease. METHODS: Ophthalmic examination, haematological screening, and ultrasound biomicroscopy. RESULTS: A 25 year old man showed grey-white, granular opacities in both corneas, with an 8 mm diameter ring configuration, and a V-shaped distribution in the anterior stroma. The surrounding corneal stroma was clear, and the tear film, the epithelium and its basement membrane, Descemet's membrane, and the endothelium were normal. Evidence of systemic disease was not found. Family members did not show corneal abnormalities. CONCLUSION: A bilateral corneal ring opacity may occur in healthy, asymptomatic, young people. These corneal rings may result from depositions of unknown origin, or possibly a rare corneal dystrophy.

Depth predictability of stromal pockets in the posterior cornea.

PURPOSE: To evaluate the predictability of the depth of stromal pockets made in the posterior cornea for the excision of anterior or posterior lamellar corneal buttons with a planned thickness. METHODS: Stromal corneal pocket dissections were created in human eye bank eyes by making a peripheral arcuate keratotomy incision at 60, 80, or 95% of central pachymetry and creating a pocket from the bottom of the incision across the cornea. Pocket depth was measured by pachymetry immediately after surgery and by light microscopy. RESULTS: Mean achieved central pocket depth differed by 0.03+/-0.03 mm from the intended depth. Variation in depth across the pocket decreased from 0.07+/-0.02 mm for pockets made at 60% of the intended depth to 0.05+/-0.01 mm for pockets made at 80% depth, and 0.04+/-0.02 mm for pockets made at 95% depth (p < 0.01). Pachymetric and histological measurements of relative pocket depth averaged 64+/-9% and 73+/-7%, respectively, for pockets made at 60% of the intended depth, 82+/-7% and 86+/-3% for pockets made at 80% depth, and 91+/-7% and 92+/-3% for pockets made at 95% depth. The difference between pachymetric and histological relative pocket depth measurements decreased with deeper pocket depth (p < 0.01). CONCLUSIONS: In the posterior cornea, stromal pockets can be created to within 30 microm from the intended depth. Variation in depth throughout the pocket decreases with deeper pocket depth. Pachymetry is a reliable method to check the achieved pocket depth during surgery; the accuracy of pachymetry readings improves with deeper pocket depth.

Refractive outcome following radial keratotomy and combined radial and astigmatic keratotomy.

PURPOSE: To determine whether the visual and refractive outcomes of combined astigmatic and radial keratotomy (AK/RK) procedures was different from that following RK for the correction of naturally occurring compound myopic astigmatism and spherical myopia. SETTING: Private professional practice, San Diego, California, USA. METHODS: The computer database of all incisional procedures performed by one surgeon over 10 years was reviewed to compare the visual acuity outcome of AK/RK and RK procedures. Enhancement procedures were excluded. Only data from the last office visits were analyzed to establish the relationship between visual acuity and type of keratotomy procedure performed. A multiple regression model was constructed, which included covariates of age, postoperative keratometric cylinder, and postoperative refraction. RESULTS: After controlling for covariates, the AK/RK population had significantly lower postoperative uncorrected visual acuity levels than the RK population (P < .03) after one operation (prior to enhancement surgery). CONCLUSIONS: Using the nomograms for myopia correction for unenhanced RK cases, combined AK and RK procedures appeared to reduce the expected visual results. Surgeons may consider modifying surgical nomograms to account for the expected spherical undercorrection that can occur when myopia and astigmatism are corrected simultaneously.

Comparison of two microkeratome systems.

BACKGROUND: Microkeratomes are currently used for keratomiluesis in situ (automated lamellar keratoplasty) for myopia and hyperopia and for laser in situ keratomileusis (LASIK). Visual and refractive complications have been reported with these refractive surgical procedures. We compared two microkeratomes in their ability to resect corneal lamellae to gain insight into possible mechanism(s) of refractive and visual complications following lamellar refractive procedures. METHODS: Using an eyebank eye model, we performed automated lamellar keratoplasty to theoretically correct 10.00 diopters (D) of myopia using the Automated Corneal Shaper, manufactured by Chiron, Inc. and the MicroPrecision microkeratome, manufactured by Eye Technology, Inc. Diameters before (wet) and after fixation, thicknesses of excised tissue, and scanning electron microscopy were measured in a masked evaluation to compare instruments. Ultrasonic corneal pachymetry and a mechanical tissue compression gauge were also used to assess thickness of excised tissue. RESULTS: The Chiron automated corneal shaper created blade chatter marks at the edges of all excisions, smaller than anticipated excision diameters, and a wide range of tissue thicknesses. In contrast, the MicroPrecision microkeratome created smoother resections of all tissues without creating blade marks; tissue diameters and thicknesses were closer to the intended dimensions compared to the Chiron automated corneal shaper. CONCLUSION: Different microkeratomes create different morphologic features as they excise corneal tissue. Differences in instrument design, mechanics of the tissue excision and blade oscillation, and instrument traverse combined with surgical skill influence the configuration of lamellar keratotomies.

Ultrastructural and immunohistochemical findings after linear excimer laser keratectomy.

BACKGROUND: One human pathology specimen has been studied previously following the use of the excimer laser for the correction of astigmatism. We report histopathologic findings following linear corneal excisions with the excimer laser. METHODS: A 193 nm excimer laser was used to create symmetrical, transverse excisions in a human eye to correct astigmatism. Three months later, a full-thickness corneal transplant was performed due to unsatisfactory refractive results. The excised corneal button was examined with light microscopy, transmission electron microscopy and immunohistochemistry. RESULTS: An area 10 to 20-micron wide was observed between the epithelial cells within the keratectomy and the sharply dissected stromal lamellae. This area stained positive for laminin and pro-collagen type III. Some epithelial cells showed processes reaching into this area. Descemet's membrane, immediately underneath the area of the keratectomy, contained atypically striated collagen fibers. CONCLUSIONS: These findings demonstrate wound healing changes similar to those reported following diamond knife keratotomy and photorefractive keratectomy for myopia. The changes in the posterior cornea are similar to those previously reported when an excimer laser beam approached Descemet's membrane.

Excimer laser effects on human corneal endothelium. Modulation by serum factor(s).

OBJECTIVE: To determine the possibility of endothelial cell damage after excimer laser ablation. METHODS: Endothelial cell densities and morphology of human corneas after photoablations or mechanical keratectomy were compared with those of the untreated mates after 1 week of culture with or without serum. RESULTS: Corneas cultured in serum-free medium after ablation to a depth of 150 microns showed endothelial cell densities reduced to 60% of untreated, mate corneas; ultrastructural analysis showed endothelial cell damage not seen in untreated mates. Corneas ablated to the same depth and cultured in serum-enriched medium showed no endothelial cell density loss, nor did corneas cultured in serum-free medium after an ablation to a depth of 50 microns or mechanical keratectomies averaging 95 microns. CONCLUSIONS: Endothelial cell loss in deep laser resections may be prevented by factor(s) in fetal bovine serum. The apparent lack of cell loss in clinical studies may be related to the protective action of similar factors in aqueous humor.

Comparison of the UniversalKeratome and the Automated Corneal Shaper.

PURPOSE: To compare the morphologic appearance and measurements of in situ keratomileusis performed with the UniversalKeratome (UK) with those done with the Automated Corneal Shaper (ACS). SETTING: Surgical suite within private practice. METHODS: Procedures were performed the same day on mate eye-bank eyes. In situ keratomileusis was done using existing nomograms for each instrument to resect a cap thickness of 160 microns and a myopic resection of 100 microns. Intraocular pressures were increased by inflating the globes with balanced salt solution and were measured with the suction fixation rings in place. The excised caps and stromal resections were measured twice independently after surgery, again after tissue fixation, and then evaluated with light and scanning electron microscopy. RESULTS: No complications were encountered. Compared with the ACS, the UK was easy to set up, use, clean, and take down. Its excised tissue dimensions were greater and more predictable, it resected a concave shaped lenticule (edges imperceptibly blending with the host stroma), and it created a smoother power resection surface and primary resection base. CONCLUSIONS: Smoother, predictable tissue resection, and simple assembly/disassembly and use give the UK an apparent advantage over the ACS. The UK corrects astigmatism and hyperopia by changing the shape of the poly(methyl methacrylate) optical insert.

Effect of incision direction on refractive outcome after radial keratotomy.

PURPOSE: To determine whether the direction of radial keratotomy (RK) incisions (centripetal versus centrifugal) affects refractive outcome. SETTING: Private ophthalmology office. METHODS: The database of a single surgeon was retrospectively reviewed. Stepwise regression was used to select significant predictors of refraction change in the population. In addition to incision direction, variables evaluated were optic zone diameter, number of incisions, patient age, corneal curvature, and planned incision depth. RESULTS: All variables except planned incision depth and corneal power affected refractive outcome. After controlling for number of incisions, optic zone diameter, and patient age, centripetal incisions decreased myopia 0.87 diopters more than centrifugal incisions. CONCLUSIONS: Our results, consistent with previous investigations, found that number of incisions, optic zone diameter, and patient age were significant predictors of refractive outcome after RK. Incision direction was also a significant predictor by itself or coupled with optic zone diameter and number of incisions, with the centripetal incision decreasing myopia more.

Histologic changes and wound healing response following 10-pulse noncontact holmium:YAG laser thermal keratoplasty.

BACKGROUND: Noncontact holmium:YAG laser thermal keratoplasty (Ho:YAG LTK) is a promising new technology for correction of hyperopia and astigmatism. We studied the acute histologic changes and wound healing response following Ho:YAG LTK performed with treatment parameters encompassing those used in clinical studies. METHODS: We performed 10-pulse noncontact Ho:YAG LTK on three human corneas 1 day before their removal at penetrating keratoplasty and on six New Zealand white rabbit corneas followed for up to 3 months. Tissues were studied with light and transmission electron microscopy and immunohistochemistry. RESULTS: The amount of acute tissue injury increased according to the pulse radiant energy. In human corneas, changes in the irradiated zones included epithelial cell injury and death, loss of fine filamentous structure in Bowman's layer, disruption of stromal lamellae, and keratocyte injury and death. In the rabbit corneas, similar acute changes were noted. By 3 weeks, epithelial hyperplasia and stromal contraction were present. Wound healing in the rabbits included repair of the epithelial attachment complex, keratocyte activation, synthesis of type I collagen, partial restoration of stromal keratan sulfate and type VI collagen, and retrocorneal membrane formation. CONCLUSIONS: Noncontact Ho:YAG LTK produces acute epithelial and stromal tissue changes and in rabbit corneas stimulates a brisk wound healing response.

Scheimpflug anterior segment photography assessment of wound healing after myopic excimer laser photorefractive keratectomy.

PURPOSE: To describe a method for analyzing Scheimpflug anterior segment images for a new measure of the cornea's response to excimer laser photoablation. SETTING: Mericos Eye Institute, Scripps Memorial Hospital, La Jolla, California. METHODS: Digitized Scheimpflug anterior segment photographs of operated and unoperated eyes were obtained in 17 patients 1 to 15 months after photorefractive keratectomy (PRK). The images were analyzed to determine their dimensions. Each imaged opacity was compared with corneal haze observed by slitlamp biomicroscopy, intended ablation depth, postoperative corneal thickness, and refractive error change. RESULTS: All postoperative corneas displayed a nonhomogeneous, meniscus-shaped pattern in the ablated area that ranged from 17 to 40% of corneal thickness. This pattern correlated poorly with intended laser ablation depth. CONCLUSION: This technique provides a new assessment of corneal response to PRK. Improvements in software analysis may facilitate quantitative assessment.

Effect of incision direction on refractive outcome after radial keratotomy.

PURPOSE: Radial keratotomy incisions can be made centripetally or centrifugally. The benefits and effects of both techniques have been disputed since American surgeons began performing RK in the late 1970s. We examined the RK databases of a single surgeon to determine if incision direction was associated with refractive outcome. METHODS: Stepwise regression was employed to select the important predictors of refraction change in the population. In addition to incision direction, variables eligible for entry into the model were optic clear zone diameter, incision number, patient age, corneal curvature and planned incision depth. RESULTS: All variables except for planned incision depth and corneal power entered the model. CONCLUSIONS: The results were consistent with previous investigations that found incision number, optic clear zone diameter and patient age important predictors of outcome. We also found incision direction to be a significant predictive variable with centripetal incisions decreasing myopia 0.6 diopters more than centrifugal incisions.

Human excimer laser keratectomy. Immunohistochemical analysis of healing.

OBJECTIVE: To analyze human corneal responses to excimer laser by immunohistochemistry. METHODS: Corneas cultured for 3 weeks after laser ablation or taken from patients 5 to 16 months after laser treatment were exposed to antibodies to beta, integrin; types VII, IV, and III collagen; fibronectin; type I procollagen; and prolyl 4-hydroxylase. Antibody distributions were compared with those of normal corneas and unablated regions of treated corneas. RESULTS: After 3 weeks, distribution of beta, integrin, and types VII and IV collagen was patchy; heavy deposits of fibronectin appeared subepithelially. Keratocytes stained for prolyl-4-hydroxylase and type I procollagen. With increasing postoperative time, fibronectin diminished, and beta 4 integrin and type VII collagen became linear, stromal staining of types III and IV collagen increased and their diminished. CONCLUSIONS: Components of basement membrane, attachment complexes, and stromal matrix are synthesized shortly after laser treatment. Changes in these elements persist for 16 months in the human cornea.