Purpose: To report two cases of Vogt-Koyanagi-Harada disease (VKH) resistant to systemic corticosteroid therapy, effectively treated with systemic cyclosporine. Case 1: A 52-year-old man diagnosed as VKH was administered oral corticosteroids (40 mg/day), following steroid pulse therapy. Since there was no significant improvement, he underwent a second course of steroid pulse therapy and oral corticosteroid administration (40 mg/day). However, there was still no improvement, and a combination therapy of both oral corticosteroids (40 mg/day) and cyclosporine 200 mg (3 mg/kg) was administered. As a result, the inflammation subsided and the dosage of the drugs was tapered successfully. Case 2: A 50-year-old man diagnosed as VKH underwent two courses of steroid pulse therapy, which did not improve significantly. We performed combination therapy of both corticosteroids and cyclosporine, similar to the case described above and obtained good results. Conclusion: Our experience of these two cases indicates that systemic cyclosporine treatment was effective in the management of VKH patients resistant to conventional systemic corticosteroid therapy.
Favorable improvement in visual function, credible, long-term sustainability are requisites for anterior eye-segment surgery of the cornea and the lens, key players in ophthalmological optics. Here we analyzed the sustainability, efficacy, and safety of anterior eye-segment surgery, using treatment data from numerous cases, observed over a long period.The effect of a pterygium on visual function is correlated with the degree of invasion of the pterygium in the central cornea. When the pterygium is quite severe, it takes a long time for visual function to stabilize after pterygium surgery. The recurrence rate is lower for incipient pterygium than for recurrent pterygium with a short recurrence period. Analysis of DNA CpG methylation in pterygium has shown that suppressors of cell proliferation are downregulated, while accelerators of cell proliferation are upregulated. Therefore, cells tend to proliferate increasingly in the following order: normal conjunctiva (lowest proliferation rate), incipient pterygium (intermediate proliferation rate), and recurrent pterygium (highest proliferation rate). These findings help elucidate pterygial pathophysiology and prevent its recurrence.In keratorefractive surgery using an excimer laser, the long-term stability of visual function remains problematic. In a long-term study of changes in postoperative visual function and corneal shape, it is noted that physiological properties, including corneal sensitivity and higher-order corneal aberrations recovered at 1 year and stabilized at 10 years after in laser in situ keratomileusis surgery. However, corneal thickness increased continuously for 10 years post-surgery, and myopia continued to increase.In keratoplasty, the transparency of the transplanted cornea and visual functions need to be sustained for a long period. In penetrating keratoplasty (PKP), the mean cumulative transparency cure rate at 12 years post-surgery was 60.4%, which was highest in cases with keratoconus and corneal dystrophy, and lowest in cases with bullous keratopathy and regraft. At 5 years post-surgery, both the cumulative transparency cure rate and postoperative visual function were more favorable in Descemet stripping automated endothelial keratoplasty (DSAEK) than in PKP. Moreover, for artificial corneas (Boston keratoprosthesis) introduced in cases of regraft, both the survival rate and postoperative visual function were more favorable in DSAEK than in PKP.A continuous increase in surface light scattering of specific intraocular lenses (IOL) has been a long-term concern. However, even with an increase in surface light scattering over a period of more than 10 years post-surgery, visual function remained largely unaffected. The observation of frozen torn surfaces of IOLs explanted from patients and unused IOLs that had undergone accelerated aging demonstrated that surface light scattering was caused by a slight phase separation of water on the surface of the IOL. Although forward scattering was not a marked component of the measured surface scattering, it was of clinical concern.Normal conjunctival bacterial flora is thought to have a protective effect against bacterial infection in daily life. However, perioperative prophylactic use of antibiotics may eliminate the normal conjunctival bacterial flora and it is unknown if, after completion of the course of antibiotics, the flora would recover to the same state as before, nor is the growth rate of the normal flora known. Therefore, we analyzed the sustainability of the normal conjunctival bacterial flora after anterior eye-segment surgery. To examine the microenvironment of the anterior eye segment, annual changes in the bacteria isolated from the conjunctival sac prior to cataract surgery were surveyed. The sensitivity of Staphylococcus epidermidis (SE) to levofloxacin (LVFX) decreased annually, indicating that normal conjunctival-sac flora has undergone a rapid increase in resistance to fluoroquinolones.The development of antibiotic resistance in conjunctival bacterial flora is a serious concern. We analyzed the recovery period of normal conjunctival-sac flora and the change in the sensitivity of SE to LVFX over time. In our study, the number of bacterial strains detected was recovered by 3 months post-surgery, while the sensitivity of SE to LVFX had not recovered to the presurgical value even by 9 months post-surgery. In addition, analysis of the effect of the antimicrobial administration period on the acquisition of resistance and the long-term recovery period of bacteria showed a faster recovery of the sensitivity in cases with 1 week of LVFX administration post-surgery compared to those with a 1-month administration.Long-term data of cases with pterygium surgery, keratorefractive surgery, keratoplasty, and IOL were analyzed scientifically. There was recovery of normal flora after perioperative use of antibiotics. Analyses of a large amount of data accumulated over a long period resulted in new findings that would not have been observed using conventional data from short-term studies. This examination of sustainability in ophthalmic surgery provides a basis for the advancement of ophthalmic surgery, but it requires routine collection of clinical data from each patient.
Glaucoma surgery is classified into a number of areas: intra-ocular drainage, filtration surgery and cyclo-coagulation. Although filtration surgery is the most effective way to lower intraocular pressure (IOP), no surgical technique manages to result in fulfills complete efficacy and safety. Trabeculectomy, one type of filtration surgery, is a common surgical procedure for glaucoma. Though trabeculectomy is fairly effective in lowering intraocular pressure, it is not rare that refractive errors remain or the patients suffer from severe surgical complications. Thus, surgical results of glaucoma surgery need to be improved. In this review, I explain the work we have done to address this issue, and discuss our results and novel trials.Our clinical studies clarified that cataract surgery affects the results of trabeculectomy to some extent. Additionally, previous vitrectomy, previous glaucoma surgery, uveitic glaucoma, neovascular glaucoma and secondary glaucoma associated with family amyloid polyneuropathy were identified as prognostic factors influencing the results of trabeculectomy. These factors may change the intraocular environment, and thereby affect wound healing following trabeculectomy, resulting in poor IOP control.Focusing on the changes in the intraocular environment caused by background factors, we examined cytokine levels in the aqueous humor. In pseudophakic eyes, even more than a year following post-phacoemulsification, the levels of proinflammatory cytokines, such as interleukin (IL)-6, IL-8, and monocyte chemoattractant protein (MCP)-1 were elevated in the aqueous humor. These cytokines have positive correlations, and remain elevated in eyes with uveitic glaucoma or neovascular glaucoma, suggesting that they exercise a combined impact on wound healing. Of those, MCP-1 in paticular had significant effect on the results of trabeculectomy.To evaluate the effects of the changes in intraocular environment on the filtering bleb after trabeculectomy, we quantitatively assessed the bleb using three-dimensional anterior OCT (3D AS-OCT). Three-dimensional imaging identified the filtration opening on the edge of the scleral flap as an aqueous route after trabeculectomy, and its function was confirmed during bleb revision surgery. Subsequent prospective study using 3D AS-OCT clarified that the filtration openings tended to close time-dependently, affecting future IOP control, and the width of the filtration openings was correlated with the level of aqueous MCP-1.To elucidate wound-healing mechanisms after trabeculectomy at a cellular level, we conducted cell biological experiments using macrophages and conjunctival fibroblasts. It is known that trans-differentiation of fibroblasts into myofibroblasts, which was induced by macrophages and other cells, is a key for the progression of wound healing process. The trans-differentiation of fibroblasts was suppressed by either ROCK inhibitors or epigenetic drugs. Using in vivo imaging with a two-photon microscope, we found that either ocular surgery or MCP-1 treatment activated subconjunctival inflammatory cells. From the viewpoint of rebalancing the pathological shift of intraocular environment, it is suggested that anti-MCP-1 therapy and CCR2 inhibitors could be novel clues assisting in the improvement of surgical results of glaucoma surgery.
Purpose: To investigate the current status of corneal and conjunctival disorders due to antitumor drugs in Japan.Methods: Questionnaires on corneal and conjunctival disorders due to antitumor drugs were sent to members of the Japan Cornea Society, and data on patients' background, clinical findings, treatment and prognosis of cases between January 2009 and December 2011 were collected and analyzed. Results: Out of all 221 cases from 66 facilities, TS-1Ⓡ had been administered in 210 cases (95.0%). Corneal findings were noted in 192 cases (86.9%), including 161cases (72.9%) of superficial punctate keratopathy, 55 cases (24.9%) of epithelial crack line, 38 cases (17.2%) of sheet-like epithelial abnormality, and 15 cases (6.8%) of corneal erosion. Conjunctival and ciliary findings were observed in 49 cases (22.2%). Lacrimal obstruction and constriction were found in 81cases (36.7%). Logistic regression analyses revealed the discontinuation and switching of antitumor drugs as the significant factor of good prognosis of clinical signs and visual acuity in cases with TS-1Ⓡ administration.Conclusions: Although corneal and conjunctival disorders due to antitumor drugs, especially TS-1Ⓡ, are important adverse effects, the only effective treatment at this time is the discontinuation and switching of antitumor drugs. Future prospective studies are needed to elucidate pathogenesis, aiming to the prediction and prevention of the occurrence.
Background: Recently, carbon ion radiotherapy (CIR) has become the standard therapy for choroidal melanoma to preserve the eyeballs in Japan. We report a case of choroidal melanoma resulting in eyeball enucleation 2 years after carbon ion radiotherapy due to local recurrence.Case: A 64-year-old man was referred to Tokyo Medical University hospital with a diagnosis of choroidal tumor. Intraocular tumor was located at the equator of temporal area in ocular fundus. After systemic work-up, clinical diagnosis of choroidal melanoma was made and CIR was applied. After CIR, the intraocular tumor was stable for 2 years. However, 2 years and 3 months after CIR, local recurrence of the tumor was detected. Eventually, the eyeball was enucleated. Histopathologically, the original lesion was composed of melanoma cells containing abundant melanin pigments, and these cells were positive for HMB-45, Melan-A and S-100 protein. In contrast, the recurrent lesion showed lack of melanin pigment and proved less positive for HMB-45, Melan-A and S-100 protein. Four months after enucleation, the patient developed liver metastasis and received the appropriate supportive care. Conclusions: Even after CIR with remission, choroidal melanoma can recur. Recurrent lesions of the tumor may reveal alternative histopathological findings compared to the original lesion.
Purpose: To report the outcomes of reconstruction of eyelids by modified Hughes method in patients with sebaceous carcinoma of the eyelid.Method: Nineteen patients were diagnosed as having sebaceous carcinoma in the Department of Ophthalmology, Tokyo medical University from 2009 through 2013. Tumors were resected and eyelids were reconstructed by the modified Hughes method. We retrospectively evaluated the patients' background and outcome of the surgery.Results: Average age of the patients was 71 years old, and average follow up period after surgery was 24 months. Average size of the tumor was 10.2 mm in upper eyelid and 7.8 mm in lower eyelid. After resection of the tumor, the defect of the eyelid was reconstructed by tarsoconjunctival flap (Hughes flap) and by stretching the surrounding eyelid skin. Pedicle was divided at an average of 33 days after surgery. Post-operative complications included mild entropion in 3 patients, ectropion in 3 patients, superficial punctate keratitis in 3 patients, and 1 ptosis that required surgical repair. One patient who showed local recurrence of the tumor underwent extended resection and reconstruction of the eyelid.Conclusion: The modified Hughes method is effective for reconstruction of the resected eyelids with sebaceous carcinoma. Especially, postoperative complications of the ocular surface tend to be limited.
Purpose: To evaluate the indications and outcomes of amniotic membrane (AM) transplantation for corneal and conjunctival diseases.Subjects and methods: Ninety-five eyes of ninety patients who underwent AM transplantation between January 2007 and May 2016 were included in this study. The surgical procedures, diagnosis and postoperative outcomes were investigated retrospectively.Results: Transplantation was conducted in three surgical procedures. AM patch, for the promotion of corneal re-epithelialization, was performed in 14 cases with persistent epithelial defects. Thirteen cases healed with total epithelialization. Corneal perforation was noted in Stevens-Johnson syndrome and cured with keratoplasty. AM graft for basement membrane supply, was performed in 72 cases. Of these, 32 cases had been followed for at least one year after AM graft out of which pterygium recurred at one year in 5. Conjunctival tumor recurred in 3 out of 17 cases, and was treated with a repeated of AM graft. AM stuff for substrate supply to the deep corneal layer, was performed in 9 cases with corneal perforation. Leakage of aqueous humor was cured in all 9 cases. Seven cases had keratoplasty performed after the AM stuff and recovered completely. The other 2 cases were observed without additional surgery. There were no complications due to the AM transplantation during the course of treatment in any of the 95 cases.Conclusion: AM transplantation is applied in three different procedures. Each of these was effective in achieving the corneal and conjunctival reconstruction designed for it.
Purpose: As the relationships between refraction and birth month suggest that day length factors affect the infantile refractive development, we aimed to prove the effect of day length factors by examining its evidence even among the elderly. Methods: We studied 1622 patients with cataracts (740 men and 882 women) who had preparatory measurements for corneal radius, axial lengths, and refractions for intraocular lens implantation. The day lengths for which each subject was exposed to from the first to eleventh month since birth were represented by variables DL1 to DL11. Similarly, absolute deviations from the yearly average of day lengths were represented by DDL1 to DDL11. We performed multiple regression analysis by substituting DL or DDL as explanatory variables for corneal radius, axial length, or refraction. Results: DLs were not relevant variables in elucidating corneal radius, axial length, and refraction. In contrast, DDLs were relevant variables in elucidating corneal radius (p<0.05). This association weakened for refraction and was not pertinent for axial length. Conclusion: Infantile refractive development is affected by the deviation in day length rather than the day length itself, evidence for which can still be observed among the elderly.
Background: Acquired peripheral retinoschisis (RS) is usually found in middle age and older patients, and is occasionally accompanies by retinal detachment (RD). In this report, a case of acquired RS with RD in a young adult is documented.Case: A 27 years old man diagnosed with RD in the right eye at a periodical examination.Findings: RD was located at upper nasal part of fundus with the margin close to the macula. Dome shaped retinal protrusion was also seen at the periphery of nasal upper retina. Optical coherence tomography revealed no macular abnormality. Following a diagnosis of RD with atrophic retinal hole, scleral buckling and SF6 gas injection were performed, but the RD was not fully resolved. Additional B mode ultrasonography visualized peripheral RS at the dome shaped retinal protrusion. To avoid macular detachment, pars plana vitrectomy was performed. After executing a posterior vitreous detachment and subretinal fluid extraction, photocoagulation was performed around the area of the RS. Consequently, both the RD and RS were completely resolved. Conclusions: Acquired RS with RD may occur in young adults. This can be successfully resolved by surgery.
Purpose: To identify indices of visual improvement after conservative treatment for branch retinal vein occlusion (BRVO) with macular edema.Methods: We retrospectively reviewed the charts of 33 eyes of 33 patients with BRVO with macular edema. Inclusion criteria were 1) onset within 4 months, 2) decimal visual acuity of 0.05 to 0.5, and 3) minimum central subfield thickness (CST) of 250 μm. After 3 months of treatment with oral aspirin and kallidinogenase, the patients were divided into two groups: those with logarithmic minimum angle of resolution (logMAR) visual improvement of 0.3 or more (14 eyes) and less than 0.3 (19 eyes). We then compared systemic and ocular findings in the groups.Results: The groups differed significantly in logMAR improvement after 1 month (p<0.01) and in CST change after 1 month (p<0.05). Multiple logistic regression analysis showed that CST change after 1 month was a significant index of visual improvement (p<0.05). The cutoff value for visual improvement was -30 μm (sensitivity: 78.6, specificity: 68.4, positive predictive value: 64.7, negative predictive value: 81.3).Conclusion: A decrease in CST of more than 30 μm 1 month after conservative treatment indicates that visual acuity is likely to be improved after 3 months.
Purpose: To determine the effect of low-dose cyclosporine (CyA) treatment for patients with chronic Vogt-Koyanagi-Harada (VKH) disease resistance to systemic corticosteroid treatment.Methods: We retrospectively evaluated patients diagnosed with chronic VKH disease resistance to systemic corticosteroid treatment at Japan Community Health Care Organization (JCHO) Osaka Hospital between March 2013 and March 2016. We followed the observation with systemic low-dose CyA (100 mg once daily) treatment of these patients. The patients were divided into two groups, anterior ocular inflammation group and posterior ocular inflammation group. Demographic data were reviewed, including age, gender, the existence of inflammation at the initial visit and three months after CyA treatment, and side effect.Results: Twenty-three eyes of thirteen patients with chronic VKH disease were included in this study (11 women, 2 men; mean age, 54.6±11.9 years). Nine cases showed anterior ocular inflammation and seven cases showed posterior ocular inflammation (includes overlapping cases). Thirteen of fourteen eyes in the anterior ocular inflammation group subsided at three months after CyA treatment, and ten of thirteen eyes in the posterior ocular inflammation group subsided at three months after treatment. We had to stop the treatment in one patient because of severe increase of serum triglyceride.Conclusions: Low-dose CyA treatment was effective in patients with chronic VKH resistance to systemic corticosteroid treatment. Our results suggest that this treatment was more effective in the anterior ocular inflammation group than in the posterior ocular inflammation group; however, a larger number of patients and longer observation periods are needed to confirm these results.
More than 90% of ocular diseases, such as glaucoma, age-related macular degeneration, and dry eye, are age-related with the incidence increasing with age. Furthermore, although retinitis pigmentosa and myopia may be associated with hereditary factors, they are also considered age-related diseases since they progress with aging. Thus, instead of targeting individual diseases, a new approach aimed at targeting aging itself is being examined.The most established current anti-aging approach is calorie restriction, considered to induce various gene expressions such as anti-oxidative enzymes contributing to life extension. At first, we confirmed that conditions under increased oxidative stresses, including genetically modified animals, such as Sod-1 knockout mice (KO), Mev1 transgenic mice, and Nrf-2 KO mice, and smoking induces a decrease in tear secretion resulting in dry eye. Recently, we found that dietary supplements containing lactoferrin or lactic acid bacteria suppress oxidative stress in the lacrimal glands, these results need to be considered in association with the current advances in the microbiome research. It is now possible to promote the clinical use of those supplements to increase tear secretion. Calorie restriction (CR) activates longevity gene sirtuins. We also have shown that agents activating sirtuins, such as resveratrol or nicotinamide mononucleotide (NMN) have retinal protective effects. Particularly, NMN is promising since we have confirmed its therapeutic effect against retinitis pigmentosa. Ketone bodies are considered another mechanistic target of CR. We developed eye drops containing ketone bodies, and confirmed a therapeutic effect similar to that of CR. Now we are expanding our investigations to include new therapies for dry eye and neuroprotection for the retina and the optic nerve. Other pathways such as endoplasmic reticulum (ER) stress, inhibition of hypoxia-inducible factor (HIF), and inhibition of the insulin-like growth factor (IGF) are also considered to be targets for the anti-aging approach.Taken together, the new strategy "anti-aging" is one approach in dealing with ocular diseases. The anti-aging approach is promising as the next generation of preventive medicine focusing on aging for the current era with increased health care expenditures.
The population of high myopia in Japan is large and increasing. It is a high risk factor not only for its specific macular complications but also as a precursor for cataracts and glaucoma. Myopic foveoschisis and the consequent macular hole with retinal detachment (MHRD) are caused by inner retinal traction which may include the vitreous cortex, epiretinal membrane, internal limiting membrane and posterior staphyloma formation. Vitrectomy is the 1st choice of treatment, and releasing the retina from traction is the goal. MHRD has poor anatomical success rates, and, therefore, inverted internal limiting membrane is a common treatment procedure to enhance MH closure. Myopic choroidal neovascularization occurs predominantly in highly myopic eyes, and anti-vascular endothelial growth factor therapy is the 1st line treatment. Normally the patient's eyes respond well, however, recurrence is an important issue. Conventional optical coherence tomography (OCT) and fluorescein angiography are the major diagnostic tools. At the same time, advanced technologies such as OCT-angiography and Polarization-sensitive OCT may enable an early and more accurate diagnosis. High myopia is a high risk factor for glaucoma and its mechanism is still uncertain. Studies using OCT thus far have shown variety of abnormalities occurring in highly myopic eyes inside and around the optic nerve head. High myopia has uncommon progression patterns such as preceding the papillo-macular bundle damage, especially in younger patients. Future studies are needed.
