- To evaluate the efficacy of topical corticosteroids in treating herpes simplex stromal keratitis in conjunction with topical trifluridine.
- To evaluate the efficacy of oral acyclovir in treating herpes simplex stromal keratitis in patients receiving concomitant topical corticosteroids and trifluridine.
- To evaluate the efficacy of oral acyclovir in treating herpes simplex iridocyclitis in conjunction with treatment with topical corticosteroids and trifluridine.
Despite the availability of antiviral agents that are effective in treating herpes simplex epithelial keratitis, inflammation in the corneal tissue and iris can lead to corneal scarring and visual impairment in many patients. Prior to the HEDS-I trials, the role of topical corticosteroids in the management of herpes simplex virus (HSV) stromal keratitis was uncertain. The value of adding an oral antiviral agent to topical corticosteroids and topical antiviral agents was also unknown.
Herpetic Eye Disease Study-I consisted of three randomized, placebo-controlled trials (1992–1996). All patients received the topical antiviral trifluridine as prophylaxis against recurrences of HSV epithelial ulceration. Patients were evaluated weekly for 10 weeks, every other week through week 16, and again at 6 months.
Herpes Stromal Keratitis, Not on Steroid Trial (HEDS-SKN): Patients with active HSV stromal keratitis who had not used a topical corticosteroid in the preceding 10 days were randomized to treatment with topical 1% prednisolone phosphate drops (8 times a day for 7 days, progressively decreased over 10 weeks to once a day) or topical placebo drops (same schedule was followed).
Herpes Stromal Keratitis, on Steroid Treatment (HEDS-SKS): Patients with active HSV stromal keratitis who already were being treated with a topical corticosteroid were randomized either to oral treatment with acyclovir (400 mg five times daily) for 10 weeks or to the identical dose of placebo capsules. Patients also received topical prednisolone phosphate in the dosage schedule described above for the SKN trial.
Herpes Simplex Virus Iridocyclitis, Receiving Topical Steroids (HEDS-IRT): Patients with active HSV iridocyclitis were randomized either to oral treatment with acyclovir (400 mg five times daily) for 10 weeks or to the identical dose of placebo capsules. Patients also received topical prednisolone phosphate in the dosage schedule described above for the SKN trial.
Patients ≥12 years, no active HSV epithelial keratitis, no prior keratoplasty of the involved eye, and not pregnant.
The primary outcome was the time to development of preset criteria for treatment failure during the 16-week period of examination.
HEDS-SKN: 106 patients were enrolled. Compared with the patients in the placebo group, the patients who received prednisolone phosphate drops had faster resolution of the stromal keratitis and fewer treatment failures. However, delaying the initiation of corticosteroid treatment did not affect the eventual outcome of the disease.
HEDS-SKS: 104 patients were enrolled. Over the 16-week follow-up period, there was no difference in the rate of treatment failure between the two groups. Thus there was no apparent benefit in the addition of oral acyclovir to the treatment regimen of a topical corticosteroid and a topical antiviral.
HEDS-IRT: 50 patients were enrolled during a 4-year recruitment period. Although the number of patients enrolled in this trial was too small to achieve statistically conclusive results, the trend in the results suggested a benefit in adding oral acyclovir to the treatment of HSV iridocyclitis in patients receiving topical corticosteroids and trifluridine prophylaxis.
- To determine whether early treatment (with oral acyclovir) of HSV ulcerations of the corneal epithelium prevents progression to the blinding complications of stromal keratitis and iridocyclitis.
- To determine the efficacy of low-dose oral acyclovir in preventing recurrent HSV eye infection in patients with previous episodes of herpetic eye disease.
- To determine the role of external factors (such as ultraviolet light or corneal trauma) and behavioral factors (such as life stress) on the induction of ocular recurrences of HSV eye infections and disease.
Ocular HSV infection can lead to corneal scarring and neovascularization, permanent endothelial dysfunction and corneal edema, secondary glaucoma, and cataract. Despite the availability of topical antiviral agents that are highly active against HSV keratitis, there is still no known effective method for reducing the frequency of recurrence or severity of stromal keratitis and iridocyclitis. In addition, the prognosis is poor for recovery of good vision following penetrating keratoplasty (PK) for actively inflamed or highly vascularized herpetic corneas.
Herpetic Eye Disease Study-II consisted of two randomized, placebo-controlled trials that assessed the role of oral acyclovir in the management of herpetic eye disease (1992–1996) and one epidemiologic study that investigated risk factors, including stress, for the development of ocular recurrences of the disease.
Herpes Simplex Virus Epithelial Keratitis Trial (HEDS-EKT): Evaluated the benefit of oral acyclovir (400 mg five times a day for 21 days) given during treatment of an acute HSV keratitis (dendritic or geographic keratitis) in preventing the occurrence of later blinding complications.
The primary outcome was the time to the first occurrence of stromal keratitis or iridocyclitis in the study eye (eye with epithelial keratitis at time of study entry).
Acyclovir Prevention Trial (HEDS-APT): Evaluated the benefit of long-term acyclovir treatment (400 mg twice a day for 1 year) in patients with a recent history of HSV eye disease but no current active disease. Episodes of recurrent HSV eye disease during the trial were treated with topical corticosteroids and antivirals as indicated, but patients continued to receive the oral acyclovir or placebo for the entire 365-day period.
To be eligible, a patient must have experienced any kind of ocular herpes simplex infection (blepharitis, conjunctivitis, keratitis, or iridocyclitis) in the preceding year. The infection must have been inactive and untreated for at least the previous 30 days.
The primary outcome was the time to the first recurrence of any type of HSV eye disease in either eye.
Ocular HSV Recurrence Factor Study (HEDS-RFS): Evaluated the effect of psychological, environmental, and biological factors on recurrence episodes of herpetic eye disease. Patients recruited into the HEDS-APT trial were eligible to participate in HEDS-RFS if they are 18 years or older. At entry, all subjects filled out a questionnaire to estimate the negative affectivity trait measure. Subjects also filled out a short questionnaire every week for 52 weeks to track acute and chronic stressors (e.g., illnesses, injuries, menstrual periods, sun exposure, and emotional and financial stress). The investigators ensured patient privacy by the patients’ mailing of the weekly logs directly to the HEDS National Coordinating Center.
HEDS-EKT: Patient recruitment was stopped after enrolment of 287 of the originally planned 502 patients because of a lack of any suggested efficacy of the treatment protocol. In the treatment of acute HSV epithelial keratitis, there was no benefit on addition of oral acyclovir to treatment with topical trifluridine in preventing the development of stromal keratitis or iritis. Importantly, the study found that the risk of stromal keratitis or iridocyclitis was quite low (much lower than the published risk in the literature) in the year following an episode of epithelial keratitis treated with topical trifluridine alone.
HEDS-APT: Of the 703 patients enrolled, 357 were randomly assigned to the acyclovir group, and 346 to the placebo group. Only 4% of patients in the acyclovir group and 5% in the placebo group stopped treatment because of side effects. One-half of these side effects were due to gastrointestinal upset; some patients may have had intolerance to the lactose contained in the study capsules (treatment medication that does not contain lactose is now available). The study concluded that prophylactic oral acyclovir reduced the probability of recurrence of any form of ocular HSV by 41%. Importantly, researchers noted a 50% reduction in the rate of return of the more severe form of the disease—stromal keratitis—among patients who had this infection during the past year.
In addition to the main findings, it was also noted that during the 12 months of treatment:
- Oral acyclovir reduced the incidence of epithelial keratitis from 11% to 9%, and the incidence of stromal keratitis from 13% to 8%.
- 4% of patients in the acyclovir group and 9% in the placebo group had more than one recurrence.
HEDS-RFS: Psychological stress does not appear to be a trigger of recurrences of ocular HSV disease. If not accounted for, recall bias can substantially overestimate the importance of factors that do not have a causal association with HSV infection.
MYCOTIC ULCER TREATMENT TRIAL (MUTT) I7
To evaluate outcomes of topical natamycin vs. voriconazole in cases of fungal corneal ulcers.
Infectious keratitis is a leading cause of monocular vision loss worldwide. Fungal keratitis is endemic in tropical regions, accounting for as many as half of all corneal ulcers. Mycotic ulcer tends to have guarded visual prognosis contributing significantly to ocular morbidity. Fungal corneal ulcers can be more difficult to treat than bacterial corneal ulcers, with worse outcomes. Prior to the onset of this study natamycin was the only FDA approved topical antifungal agent in ophthalmology; though the use of topical voriconazole had been documented in few reports. The role of topical voriconazole in treatment of mycotic corneal ulcer and its comparison with topical natamycin was not studied in a randomized controlled trial.
Mycotic Ulcer Treatment Trial I (2013) was a National Eye Institute-supported, randomized, double-masked, active comparator-controlled multicentric interventional trial. The enrolled participants were randomized into two groups based upon the therapy they received into topical natamycin 5% and topical voriconazole 1%. The patients were advised to use the topical medication one drop every hour while awake for the first week followed by every 2 hourly till 3 weeks.
Patients above 16 years of age that presented with smear positive filamentous fungal keratitis (KOH wet mount, Giemsa or Gram stain) with a visual acuity in between 20/40 and 20/400 in the affected eye were included. Patients presenting with an impending perforation, bilateral corneal ulcers, visual acuity worse than 20/200 in nonaffected eye or those with mixed infections such as viral, bacterial, or acanthamoeba keratitis were excluded.
- The primary outcome measure was the best spectacle corrected visual acuity (BSCVA) at 3 months in terms of log MAR.
- The secondary outcome measures were BSCVA at 3 weeks, time to re-epithelialization, size of infiltrate or the scar at 3 weeks and 3 months, microbiological cure at 6 days, corneal perforation and/or the need full-thickness therapeutic keratoplasty.
The trial suspended recruitment after 323 patients as per recommendations of Data Safety and Monitoring Committee based on higher perforations/therapeutic keratoplasty occurring in voriconazole group (n = 34) compared to natamycin group (n = 18) (p = 0.02).
- The most commonly identified organism was the Fusarium species (40% cases) followed by Aspergillus species (17% cases).
- The median duration of follow-up was 31 days in natamycin group and 39 days in voriconazole group.
- At 3 months visual acuity was worse by 1.8 lines in voriconazole group as compared to natamycin group. The mean BSCVA for Fusarium species was 4.1 lines better in natamycin prescribed group as compared to the voriconazole group.
- The mean BSCVA was 0.49 log MAR in natamycin treated group and 0.60 log MAR in voriconazole treated group at 3 weeks follow-up.
- 48% patients in the voriconazole group had culture positive at 6 days in contrast to 15% in natamycin treatment arm. Subgroup analysis revealed higher percentage in the Fusarium group.
- The scars were smaller in Fusarium only group in the natamycin treated arm at 3 months follow-up, but no such difference was noted in the non-Fusarium group.
- Perforation of ulcer with or without therapeutic keratoplasty was seen in 34 patients in voriconazole group and only 18 in natamycin treatment group.
MYCOTIC ULCER TREATMENT TRIAL (MUTT) II8
To assess the role of oral voriconazole therapy as compared to placebo as an adjunct to topical antifungal agents in filamentous fungal keratitis.
Mycotic Ulcer Treatment Trial I demonstrated better response of filamentous mycotic ulcers to topical natamycin 5% than topical voriconazole 1%. This result was attributed to subtherapeutic drug levels achieved in the tissue after intermittent topical drug use by the authors. Oral voriconazole has good ocular penetration and may provide consistent tissue drug levels especially in deep mycotic infections. Thus MUTT II investigated the role of adjuvant oral voriconazole therapy.
Mycotic Ulcer Treatment Trial II (2016) was a National Eye Institute-funded, placebo-controlled, double-masked, randomized clinical trial where in effect of oral voriconazole vs. placebo was studied in severe fungal corneal ulcer. The enrolled participants initially received topical 1% voriconazole, but after the results of MUTT I topical natamycin 5% was added in both arms. One group received oral voriconazole and second group received placebo drug.
Smear positive filamentous fungal keratitis patients with a vision of 20/400 or worse were enrolled for the study. Patients excluded were those with bilateral ulcers, coinfection, vision <20/200 in fellow eye, impending perforation, pregnancy, weight <40 kg or younger than 16 years.
The primary outcome was to measure the rate of ulcer perforation and/or therapeutic keratoplasty within 3 months of inclusion. Secondary outcomes were measure of BSCVA at 3 weeks and 3 months, infiltrates and/or scarring at 3 weeks and 3 months, time to re-epithelialize, microbiological cure at 6 days and complications.
- A total of 240 patients from India and Nepal were enrolled, out of which follow-up (3 months) data for only 207 patients was available.
- Of the 119 patients (49.6%) in the oral voriconazole treatment group, 65 were male (54.6%), and the median age was 54 years (interquartile range, 42–62 years).
- 46.2% perforations occurred in the placebo arm and 53.8% in the oral voriconazole group. There was no statistically significant difference in both groups in the rate of perforation and need for therapeutic PK [hazard ratio: 0.82; 95% confidence interval (CI): 0.57–1.18; p = 0.29].
- The mean BSCVA and size of infiltrate and/or scar was comparable at 3 weeks and 3 months.
- No significant difference was noted in microbiological cure (culture positivity at 6 day) amongst both groups.
- The adverse events were more in oral voriconazole group (48.7%) vs. placebo group (23.1%).
- There was a significant increase in the voriconazole-associated adverse effects such as elevated liver enzymes and visual hallucinations.
STEROID IN CORNEAL ULCERS TRIAL (SCUT)9
To determine the effect of topical corticosteroids as adjunctive therapy in bacterial keratitis to improve long-term clinical outcomes.
The use of topical steroids in cases of bacterial keratitis is potentially controversial with different studies suggesting variable outcomes. While anti-inflammatory action of steroids may decrease scarring and improve visual outcomes of bacterial keratitis there exist a potential risk of exacerbation of the pre-existing infection and secondary complications. There is lack of substantial evidence to support their use in cases of bacterial keratitis for long-term clinical improvements.
Steroid in Corneal Ulcers Trial (2012) is a National Eye Institute-funded, double-masked, placebo controlled, randomized multicentric clinical trial comparing placebo vs. topical corticosteroids in patients receiving treatment for bacterial keratitis. A total of 500 culture positive patients of bacterial keratitis after receiving 48 hours of topical moxifloxacin 0.5% were randomized to receive either topical prednisolone phosphate 1% or placebo. The steroids were administered as 1 drop 4 times per day for 1 week, then twice a day for 1 week, and then once per day for 1 week.
Culture-proven patients of bacterial keratitis were recruited. All eyes with perforated corneal ulcer, impending perforation, evidence of fungal, and viral or acanthamoeba keratitis were excluded. Patients with previous PK, use of steroids during the course of present ulcer, or fellow eye vision lower than 6/60 were not included in the study.
The primary outcome was BSCVA at 3 months. Other measures were the size of the scar at 12 months.
- At 12 months follow-up a total of 399 patients were assessed.
- There was no significant difference in clinical outcomes in steroid vs. placebo group at 3 months.
- No significant difference was seen in BSCVA at 3–12 months.
- Further analysis in non-Nocardia ulcer group demonstrated one-line difference (improvement) in BSCVA in steroid group vs. placebo arm at 12 months. No such difference was seen in Nocardia ulcers.
- Steroids were also associated with a larger scar size in Nocardia ulcer group.
- There was no significant difference in the rate of healing between treatment arms among patients whose re-epithelialization occurred within 21 days from enrolment. However, among patients with an epithelial defect at 21 days or later from enrolment, a higher proportion had received corticosteroids.
- To describe the clinical course of keratoconus and to describe its visual and physiological manifestations, including high- and low-contrast visual acuity, corneal curvature, slit lamp biomicroscopic findings, corneal scarring, and quality of life.
Previous large-scale studies of keratoconus focused on incidence and prevalence, etiology, or clinical management of keratoconus. Few studies have characterized the course of the disease and risk factors for its progression in large number of keratoconus patients. The incidence of vision-threatening corneal scarring in keratoconus is unknown.
Prospective, multicenteric, natural history cohort study of 1,209 patients with mild-to-moderate keratoconus followed up for 8 years (1995–2004).
Patients with keratoconus ≥12 years; Vogt's striae, Fleischer's ring, or corneal scarring characteristic of keratoconus in at least one eye.
Patients were examined annually for visual acuity, patient-reported quality of life, manifest refraction, keratometry, photo documentation of cornea (to identify central corneal scarring), photo documentation of the flattest contact lens that just clears the cornea, slit lamp biomicroscopy, and corneal topography. In rigid contact lens wearers, the fluorescein pattern of the patient's habitual contact lens was documented.
- Keratoconus patients are generally rigid gas permeable contact lens wearers with moderately steep corneas.
- Advanced keratoconus (steeper average keratometric reading) was associated with a greater likelihood of Vogt's striae, Fleischer's ring, and/or corneal scarring.
- The study group had asymmetric keratoconus. More the severity of disease, more the asymmetric disease status. Patient-reported unilateral eye rubbing, unilateral eye trauma was associated with steeper cornea. Asymmetric refractive spherical equivalent predisposes them to functional difficulties owing to reduced stereopsis.
- Central corneal scarring is associated with decreased vision, and increased glare. Contact lens wear increased the risk of incident scarring in keratoconus more than twofold. It is implied that corneal scarring might be reduced by modifying the contact lens fit.
- Over 7 years of follow-up, CLEK subjects exhibited a slow but clear decrease in their best-corrected visual acuity (vision under low-contrast conditions decreasing more rapidly than vision under high-contrast viewing conditions). Better best-corrected visual acuity, steeper corneal curvature, and fundus abnormalities were predictive of greater acuity loss with time.
- Progression of disease as measured by changes in visual acuity and corneal curvature resulted in continued decline in vision-related quality of life albeit this effect on vision-specific quality of life is worse than expected based on the condition's relatively low prevalence and clinical severity.
- There was no difference in self-reported contact lens comfort between patients fitted with apical touch vs. apical clearance. No association was found between disease severity and contact lens discomfort.
- After controlling for disease severity in the form of corneal curvature, a keratoconic eye fitted with a rigid contact lens resulting in an apical touch fluorescein pattern did not have an increased risk of being scarred centrally at baseline. This “natural history” sample cannot determine causal proof that one method of fitting lenses is safer than another. To achieve this, a randomized clinical trial is needed.
- Increased likelihood of PK was associated with corneal scarring, steeper keratometry values, poorer visual acuity, and poorer contact lens comfort. CLEK study for the first time reported an increased risk of PK associated with younger age, worse vision-related quality of life, and flatter contact lens fits.
To determine the effect of histocompatibility matching and crossmatching of corneal transplant donors and recipients on the survival of corneal graft in high-risk patients.
Histocompatibility antigen matching and/or cross matching may have offered these patients an improved chance for successful outcome.
Two multicenter double-masked, controlled, clinical trials (1986-1989) consisting of 400 patients each with a follow-up of 3 years.
- The Cross Match Study was a randomized study assessing the effectiveness of cross matching in preventing graft rejection among high-risk patients with lymphocytotoxic antibodies.
- The Antigen Matching Study was a prospective, observational study to assess the effectiveness of human leukocyte antigen (HLA)-A, B, and donor-recipient (D-R) matching in high-risk patients who had no lymphocytotoxic antibodies.
Blood samples from each enrolled patient were sent to the local CCTS tissue typing laboratory for HLA typing, and serum samples were sent to the Central Laboratory to be screened for preformed lymphocytotoxic antibodies. Depending on the results of the testing, patients were entered into the Crossmatch Study or the Antigen Matching Study. Patients in the Crossmatch Study received a cornea from either a positively cross matched donor or a negatively cross matched donor. Patients in the Antigen Matching Study received a cornea with 0 to 6 matched antigens.
Transplant patients were followed intensively during the first month after surgery. The number of clinic visits was tapered to 2 during the third and final year of follow-up, resulting in a total of 17 postoperative visits. Standard postoperative treatment regime, recognition and treatment of immunologic allograft reactions were developed and used.
Males and females aged 10 years or older with two to four quadrants of corneal stromal vascularization or a history of allograft rejection in the eye considered for surgery were eligible for both studies in the CCTS. Patients with conditions that would increase the risk of nonrejection graft failure, such as xerophthalmia or severe exposure keratopathy and patients with systemic diseases or with medication usage that might alter their immune response were excluded.
Irreversible failure of the corneal allograft due to all causes was the primary outcome variable in both studies. Allograft reaction episodes, irreversible failure due to rejection, and visual acuity were secondary outcome variables.
- Donor-recipient tissue typing had no significant long-term effect on the success of corneal transplantation.
- Data from the CCTS indicate that matching patient and donor blood types combined with treating patients with high-dose topical steroids after surgery may be potentially more effective in improving high-risk corneal transplantation. These two inexpensive strategies are considerably more economical than the more expensive donor-recipient tissue typing.
- To determine long-term graft failure rate following keratoplasty when utilizing corneas from donors over 65 years of age in comparison to younger donors.
- To assess the relation between donor/recipient ABO compatibility and graft rejection.
- To assess if the corneal endothelial cell density (ECD) is an indicator of corneal health [in an optional Specular Microscopy Ancillary Study (SMAS)].
Whether donor age should be used to determine suitability of a cornea for transplantation has been controversial. Before the onset of this study there existed a surgeon bias toward preference for younger tissues for keratoplasties in view of better outcomes. This study was designed to assess the role of donor age in long-term corneal graft survival. The SMAS was developed to evaluate the effect of donor age on endothelial cell loss (ECL) during the 5 years after PK in the Cornea Donor Study (CDS) population.
It was a prospective, multicentric, intervention cohort study with triple masking (participant, investigator, assessor of outcomes). The study enrolled 1,101 patients (11 excluded due to ineligible diagnosis) between 2000 and 2002 and included 105 surgeons at 80 sites. 43 participating eye banks provided corneas with donor age range of 12–65 years and 65–75 years of age with endothelial cell densities of 2,300 to 3,300 cells/mm2. The results were assessed at 5-year and 10-year follow-up.
Any patient in the age group of 40–80 years with significant corneal disease (endothelial dysfunction, such as pseudophakic corneal edema, Fuchs’ dystrophy, posterior polymorphous dystrophy, endothelial failure from another cause, interstitial keratitis—nonherpetic type, or perforating corneal injury).
- Primary outcome was incidence of graft failure.
- Secondary outcome measure was to measure ECD.
- Graft failure was not affected by type of retrieval, tissue processing, time between death and retrieval or between retrieval and utilization, donor characteristics (including age), and characteristics of donor cornea.
- Graft failure was higher (fourfold) in eyes undergoing keratoplasty for postcataract surgery decompensation/bullous keratoplasty (irrespective of lens status) and previous history of glaucoma surgery.
- Preoperative ECD did not affect graft failure occurring secondary to endothelial decompensation. Lower 6-month ECD correlated with graft failure. Irrespective of donor age, ECL was substantial over the first 5 years even after successful transplant.
- Higher ECD at 5 years was seen in those cases with larger grafts, female donors, and younger donor age.
- ABO blood group incompatibility was not associated with risk of graft failure.
- Donor age did not affect the graft survival. The 5-year survival rate for corneas 12–65 years and >65 years was comparable (86%).
- Dual-grading and adjudication procedures produce reliable and reproducible assessments of ECD.
- Graft failure rates were 12% ± 4% among eyes with no rejection in the first 5 years, 17% ± 12% in eyes with at least one probable rejection episode, and 22% ± 20% in eyes with at least one confirmed rejection episode.
- Preoperative history of glaucoma, particularly previous glaucoma surgery and use of antiglaucoma medications at the time of transplant were associated with risk of graft rejection.
- 10-year graft failure was higher in eyes with pseudophakic/aphakic decompensation, previous history of glaucoma or glaucoma surgery, older recipient age, history of smoking, and African American race.
- Rate of ECL at 10 years was slightly higher with age of graft as compared to lower age donors.
DREAM STUDY (DRY EYE ASSESSMENT AND MANAGEMENT)27
To evaluate the role of oral omega-3-fatty acid supplements in patients with dry eye disease (DED).
Dry eye disease is a multifactorial disease of the tear film and ocular surface characterized by alteration of the tear film homeostasis. The omega-3-fatty acids are believed to have potential anti-inflammatory action which help break the cycle of chronic inflammation. This trial was designed for evaluating the efficacy and safety of long-term oral omega-3-fatty acids supplementation in DED.
It was a prospective, multicentric, randomized, double-masked “real world” clinical trial (2018). A total of 535 subjects were randomized in a ratio of 2:1 to omega 3 or placebo arm of the trial. A year long course of treatment was given. Participants were instructed to take five capsules per day. Each active capsule contained 400 mg EPA (eicosapentaenoic acid) and 200 mg DHA (docosahexaenoic acid), providing a daily dose of 3,000 mg omega 3 (2,000 mg EPA + 1000 mg DHA) while placebo arm received 5,000 mg olive oil. The patients were examined at 3, 6, and 12 months.
Patients ≥18 years of age with dry eye for at least 6 months and Ocular Surface Disease Index (OSDI) ≥25 were recruited.
Primary outcome was change in the dry eye symptoms based upon the OSDI score.
- The mean OSDI scores were not significantly different between the omega 3 and placebo group.
- There was no significant change in cornea staining, conjunctival staining, and Schirmer's score between the two groups.
- No significant difference in clinical outcomes were noted in both groups.
- To determine whether radial keratotomy (RK) is effective in reducing myopia.
- To detect complications of the surgery.
- To discover patient characteristics and surgical factors affecting the results.
- To determine the long-term safety and efficacy of the procedure.
The study, involving 435 patients recruited 1981–1983, was a clinical trial designed to evaluate the short- and long-term safety and efficacy of one technique of RK. The surgical technique was standardized, consisting of eight centrifugal radial incisions made manually with a diamond micrometer knife. The diameter of the central, uncut, clear zone was determined by the preoperative spherical equivalent cycloplegic refraction (−2.00 to −3.12 D = 4.0 mm; −3.25 to −4.3 D = 3.5 mm; −4.50 to −8.00 D = 3.0 mm). The blade length, which determined the depth of the incision, was set at 100% of the thinnest of four intraoperative ultrasonic corneal thickness readings taken paracentrally at the 3−, 6−, 9−, and 12-o'clock meridians just outside the mark delineating the clear zone. The incisions were made from the edge of the trephine mark to the limbal vascular arcade and were spaced equidistantly around the cornea.
Patients were examined preoperatively and after surgery at 2 weeks, 3 months, 6 months, annually for 5 years, and at 10 years. Examinations in the morning and evening of the same day were done at 3 months, 1 year, 3 years, and 11 years in a subset of the patients to test for diurnal fluctuation of vision and refraction.
All participants were ≥21 years, had 2–8 diopters (D) of simple myopia correctable to 20/20 or better with glasses or contact lenses and stability of their myopia documented by previous records. Each patient agreed to have surgery on one eye and to wait 1 year for surgery on the other eye. Patients with systemic diseases that might affect corneal wound healing and patients with high corneal astigmatism were excluded from the study.
The primary outcome variables measured at each visit was the uncorrected and spectacle-corrected visual acuity and the refractive error with the pupil dilated and undilated. The corneal shape was measured with central keratometry and photokeratoscopy. Endothelial function was evaluated using specular microscopy. A slit-lamp microscope examination was made to check for complications from the incisions. Contrast sensitivity was tested in a subset of patients. Patient motivation and satisfaction were studied with psychometric questionnaires at baseline, 1 year, 5–6 years, and 10 years.
- The 10-year follow-up PERK study results confirmed that RK reduced myopia but that the effectiveness of the outcome varied among patients.
- These 10-year examinations indicated that the refractive error had not been stable in these eyes during the postoperative interval. There was a mean change in a hyperopic direction of +0.87 D between 6 months and 10 years after surgery. The average rate of change was 0.21 D per year between 6 months and 2 years, and +0.06 D per year between 2 and 10 years after surgery. Between 6 months and 10 years, the refractive error of 43% eyes changed in the hyperopic direction by 1.00 D or more. The hyperopic shift was statistically associated with incision length, with smaller clear zone diameters, and larger overall cornea diameters being associated with a greater change in refraction.
- Few patients lost spectacle-corrected visual acuity, indicating RK is reasonably safe; and that patients’ acceptance is extremely high, with the majority stating they would have the surgery again.
- The study demonstrated that for patients to be free of distance optical correction, a refraction within 0.50 D of emmetropia or a visual acuity of 20/20 in at least one eye was necessary.
PIONEER STUDY—PROSPECTIVE INTRAOPERATIVE AND PERIOPERATIVE OPHTHALMIC IMAGING WITH OPTICAL COHERENCE TOMOGRAPHY31
To assess feasibility, safety, and utility of intraoperative optical coherence tomography (iOCT) in patients undergoing ophthalmic surgeries.
Optical coherence tomography allows high-resolution imaging of ocular tissues in 2 and 3 dimensions providing valuable cross-sectional anatomic information which has revolutionized clinical management of ophthalmic diseases. Integration of OCT in surgical environment can have profound implications in surgical management of ophthalmic diseases.
This was a prospective, single-center, multisurgeon, consecutive, case series (2014). Intraoperative OCT was done using Bioptigen SDOIS portable spectral domain OCT (probe stabilized with microscope mount system or with handheld scanning). Procedure-specific imaging protocol was used for anterior and posterior segment surgeries. Surgeon feedback form was recorded immediately after surgery to assess utility of iOCT. 531 eyes were enrolled (275 anterior segment cases and 256 posterior segment surgical cases) over 24 months.
Patients over 18 years requiring ophthalmic surgery. Exclusion criteria included any media opacity that precluded OCT scanning of the area of interest and inability to provide written informed consent.
Impact of iOCT on surgical decision-making, time implications of iOCT, and adverse events specifically related to iOCT were recorded.
- Successful imaging was obtained in 98% at some point during the surgical procedure with variable image quality.
- In the anterior segment group, 275 eyes were enrolled, and common surgical procedures performed were DSAEK, phacoemulsification, femtosecond-assisted phacoemulsification, and DALK.
- Role of iOCT in anterior segment surgical decision-making:
- Graft apposition monitoring until optimal fluid removal was achieved.
- Graft dislocation rate on postoperative day 1 was 3%.
- DALK: Provided depth-related information regarding extent of trephination and residual bed information
- Phacoemulsification: Allowed assessment of location of intraocular lens and wound architecture
- INTACS: Assessment of location of implant
- 256 eyes were included in posterior segment group, with nearly all eyes requiring vitrectomy and 15 eyes requiring scleral buckling with vitrectomy.
- Common surgical procedures were epiretinal membrane (ERM) removal, full thickness macular hole (FTMH), rhegmatogenous retinal detachment (RRD), proliferative diabetic retinopathy, and vitreous hemorrhage.
- Role of iOCT in posterior segment surgical decision-making:
- FTMH: To identify changes in hole architecture, residual ILM, expansion between the ellipsoid zone and RPE after peeling.
- RRD: To identify residual subretinal fluid.
- Surgery to relieve vitreomacular traction—confirmation of release of traction and identification of newly formed FTMH.
- Overall, the median number of scan sessions per case was 2 (range: 1–5 sessions) with 6 median total scans (range: 1–24 scans). The overall median time to obtain the first image after pausing surgery was 1.7 minutes (range: 0.3–12.4).
- Overall median time surgery was paused to perform intraoperative OCT imaging was 4.9 minutes (range: 0.4–26.7) with a median duration surgery paused per scanning session of 2.8 minutes.
- No adverse events were reported.
- Wilhelmus KR, Gee L, Hauck WW; Herpetic Eye Disease Study. A controlled trial of topical corticosteroids for herpes simplex stromal keratitis. Ophthalmology. 1994;101:1883–96.
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