Impact of photodynamic inactivation (PDI) using the photosensitizer chlorin e6 on viability, apoptosis, and proliferation of human corneal endothelial cells

Background

Photodynamic inactivation (PDI) may be a potential alternative in case of therapy-resistant infectious keratitis. PDI using the photosensitizer chlorin e6 (Ce6) with high photosensitizing efficacy offers a valuable option, also for keratitis. The purpose of our study was to determine the impact of PDI with the photosensitizer Ce6 on viability, apoptosis, and proliferation of human corneal endothelial cells (HCECs), in vitro.

Methods

Human corneal endothelial cell line was cultured in DMEM/Ham’s F12 medium supplemented with 5 % fetal calf serum. HCECs cultures underwent illumination using red (670 nm) light for 13 min following exposure to 50–500 nM concentrations of Ce6 in the culture medium. Twenty-four hours after PDI, cell viability was evaluated by the Alamar blue assay, total DNA content of the cells and apoptosis using the APO-DIRECT? Kit, and cell proliferation by the BrdU Cell Proliferation Assay Kit.

Results

Using Ce6 or illumination only, we did not detect significant changes of cell viability, apoptosis, and proliferation. Following PDI, viability and total DNA content of HCECs decreased significantly above 150 nM Ce6 concentration (P?<?0.01; P?<?0.05). The percentage of apoptotic HCECs increased significantly from 250 nM Ce6 concentration (P?<?0.01), and proliferation of endothelial cells decreased significantly (P?<?0.05) above 100 nM concentration of Ce6 after PDI.

Conclusions

Photodynamic inactivation using Ce6 decreases viability and proliferation, and also triggers apoptosis of HCECs in vitro. PDI using the photosensitizer Ce6 may be a potential treatment alternative in infectious keratitis. However, to avoid endothelial cell damage, the photosensitizer must not penetrate the endothelium.     

IL-1α, IL-1β, IL-6, and IL-8 secretion of human keratocytes following photodynamic inactivation (PDI) in vitro

Purpose

With increasing resistance of microorganisms to antibiotics, photodynamic inactivation (PDI) may also be a potential therapeutic option in infectious keratitis. As part of the inflammatory response in infectious keratitis, keratocytes produce various interleukins. The purpose of this study was to evaluate the potential anti-inflammatory effect of PDI, analyzing interleukin-1 alpha (IL-1α), interleukine-1 beta (IL-1β), interleukin-6 (IL-6), and interleukin-8 (IL-8) secretion of human keratocytes following PDI, in vitro.

Methods

Primary human keratocytes were isolated by digestion in collagenase A (1.0 mg/ml) from human corneal buttons, and cultured in DMEM/Ham’s F12 medium supplemented with 10 % FCS. Keratocyte cell cultures underwent illumination using red (670 nm) light for 13 min following exposure to 100 nM concentration of the photosensitizer chlorin e6 (Ce6) in the culture medium. Five and 24 hours after PDI, secretion of IL-1α, IL-1β, IL-6, and IL-8 was measured by enzyme-linked immunoabsorbent assay (ELISA).

Results

The secretion of IL-1α was under the measurement limit in treated and untreated cell cultures 5 and 24 h after PDI. Compared to untreated controls, IL-6 and IL-8 secretion of keratocytes decreased (p?<?0.05 and 0.0001) significantly 5 hours after PDI, whereas IL-1β secretion remained unchanged. Twenty-four hours after PDI, secretion of IL-1β, IL-6, and IL-8 did not differ significantly from untreated controls.

Conclusions

In the short term, PDI does not have an impact on IL-1α and IL-1β secretion of keratocytes, in vitro. Photodynamic inactivation inhibits IL-6 and IL-8 secretion of keratocytes transiently (5 h), which normalizes 24 h following treatment. Through the short-term impact of chlorine e6-PDI on IL-6 and IL-8 secretion, PDI may inhibit the inflammatory cascade in at least keratocyte cultures.     

Long-term outcomes of unilateral orbital fat decompression for thyroid eye disease

Background

The aim of this study was to evaluate the long-term outcomes after unilateral orbital fat decompression in patients with thyroid eye disease.

Design

Retrospective, comparative, cross-sectional study

Participants

Thirty-three orbits of 33 patients were included in this study. Of the 33 patients, 13 underwent fat decompression (group A), and the other 20 had bony decompression (group B).

Methods

The medical records of patients who underwent orbital decompression to reduce proptosis for thyroid eye disease were retrospectively reviewed. The degrees of proptosis were measured by Hertel exophthalmometry preoperatively and over a follow-up period of more than 3 years. We evaluated the change in proptosis after surgery.

Main outcome measures

Postoperative change in exophthalmos.

Results

A recurrence in proptosis from fat decompression was seen in ten patients (76.9 %) in group A and in only two patients (10 %) in group B. The amount of regression due to surgery after 3 years was 2.3 ± 1.4 mm and 0.7 ± 0.9 mm in groups A and B respectively. The tendency of regression was more prominent in group A than in group B.

Conclusion

The long-term effect of unilateral orbital fat decompression for the reduction of proptosis in patients with thyroid eye disease may be weak, leading to regression. Care should be taken when determining the extent of fat decompression with consideration for this tendency.     

Antibody Array-Generated Cytokine Profiles of Tears of Patients with Vernal Keratoconjunctivitis or Giant Papillary Conjunctivitis

Purpose

To investigate differences in the cytokine and chemokine profiles of patients with vernal keratoconjunctivitis (VKC) or giant papillary conjunctivitis (GPC).

Methods

The study included six patients (six eyes) with VKC, five patients (five eyes) with GPC, and five healthy volunteers (five eyes) as controls. None of the patients had received any anti-allergic treatment prior to this study. One patient with VKC was given a tear examination to evaluate the effect of anti-inflammatory treatment with a steroid on the tear cytokine profile about the treatment. Tear samples were collected with the Schirmer I method, using filter paper. Tear samples were eluted and analyzed by an antibody array system for inflammation-related factors, including cytokines and chemokines.

Results

In the patients with VKC, four inflammation-related factors, eotaxin, interleukin (IL)-11, monocyte chemoattractant protein (MCP)-1, and macrophage-colony stimulating factor (M-CSF) increased to four times the values in the control group, and seven inflammation-related factors, eotaxin-2, IL-4, IL-6, interleukin-6 soluble receptor (IL-6sR), IL-7, macrophage inflammatory protein (MIP)-1δ, and tissue inhibitor of metalloproteinases (TIMP)-2, increased to eight times the control values. In the patients with GPC, three inflammation-related factors, IL-6, M-CSF, and monokine-induced gamma interferon (MIG), increased to four times those in the control group, and five inflammation-related factors, eotaxin-2, IL-6sR, IL-11, MIP-1δ, and TIMP-2, increased to eight times the control values. The increase in IL-6sR relative to the controls was statistically significant in both the VKC and GPC groups. The increase in eotaxin-2 was significant only in the VKC group, and that in TIMP-2 was significant only in the GPC group, compared with the controls.

Conclusions

The present study demonstrated the presence of crucial cytokines, soluble cytokine receptors, and chemokines in tears of patients with VKC and GPC. In particular, IL-6sR increased significantly in both the VKC and GPC groups, whereas eotaxin-2 increased significantly only in the VKC group. Thus, IL-6sR may play an important pathophysiological role in giant papillary proliferation in VKC and GPC, and eotaxin-2 may play an important role in eosinophilic inflammation in VKC.?Jpn J Ophthalmol 2006;50:195–204 © Japanese Ophthalmological Society 2006     

Combined clear cornea phacoemulsification in the treatment of pseudoexfoliative glaucoma associated with cataract: significance of trabecular aspiration and ab interno trabeculectomy

Background

In the present study, the effectiveness of combined cataract surgery and ab interno trabeculectomy (Trabectome) in exfoliation glaucoma (PEX) was compared with combined cataract surgery and trabecular aspiration.

Methods

In this retrospective comparative cohort outcome study, 27 consecutive patients (mean age 73.41 years?±?10.78) in group 1 suffering from visually significant cataract and PEX glaucoma (mean preoperative IOP 23.41 mmHg?±?5.86) were treated with phacoemulsification combined with Trabectome; and 28 consecutive patients (73.83 years?±?8.94) were treated with phacoemulsification combined with trabecular aspiration (mean preoperative IOP 22.22 mmHg?±?6.33). The intraocular pressure (IOP) and the number of antiglaucoma eyedrops before and after surgery were evaluated.

Results

Examinations were performed prior to surgery, 1 day, 6 weeks, 3 months, 6 months, and 1 year after surgery. In both groups there was a statistically significant decrease in postoperative IOP during the whole follow-up period. Comparing the two groups, there was a statistically significant lower IOP in the Trabectome group 1 day (p?=?0.019), 6 months (p?=?0.025), and 1 year (p?=?0.019) after surgery. Between the two groups, there was no statistically significant difference in the number of antiglaucoma eyedrops at any time.

Conclusions

Both procedures have the ability to significantly lower the postoperative IOP during the first year. However, clear cornea phacoemulsification combined with Trabectome seems to be more effective in IOP reduction in cases of PEX glaucoma associated with cataract.     

Long-term intraocular pressure changes after vitrectomy for epiretinal membrane and macular hole

Background

To investigate long-term intraocular pressure (IOP) changes after vitrectomy for epiretinal membrane (ERM) or macular hole (MH).

Methods

We retrospectively reviewed the medical records of 57 eyes with ERM and 61 eyes with MH that underwent vitrectomy. IOP levels and changes at 1, 3, 6, 12 months, and the final visit from baseline were evaluated in vitrectomized eyes and non-vitrectomized fellow eyes.

Results

In the ERM group, the mean follow-up period was 29.3 months; the mean preoperative IOP in the operated eyes was 12.9?±?2.5 mmHg and the final IOP was 13.2?±?2.9 mmHg. In the MH group, the mean follow-up period was 25.6 months; the mean preoperative IOP in the operated eyes was 13.3?±?2.5 mmHg and the final IOP was 14.0?±?3.2 mmHg. The mean final IOP of the fellow unoperated eyes was 13.0?±?2.5 mmHg in the ERM group and it was 12.9?±?3.2 mmHg in the MH group. A significant difference was found between the operated eyes and fellow eyes at the final visit in the MH group (P?<?0.01) but not in the ERM group (P?=?0.40). MH group was significantly at high risk of IOP increase after vitrectomy (P?<?0.01).

Conclusions

IOP increase after vitrectomy was found in some eyes with MH during long-term follow-up but it was unlikely in eyes with ERM.     

Influence of Selective Laser Trabeculoplasty (SLT) on combined clear cornea phacoemulsification and Trabectome outcomes

Background

In this retrospective comparative cohort outcome study, the influence of Selective Laser Trabeculoplasty (SLT) on combined clear cornea phacoemulsification and ab interno trabeculectomy (Trabectome) outcomes in Primary Open Angle Glaucoma (POAG), Pseudoexfoliation Glaucoma (PEX), and Pigmentary Glaucoma (PG) was examined.

Methods

Combined clear cornea phacoemulsification and Trabectome were performed in 27 consecutive patients with POAG, in 27 patients with PEX, and in 20 patients with PG. Each group was divided into two subgroups including patients without SLT treatment prior to surgery and patients who had insufficient response to 360° SLT treatment three months prior to surgery.

Results

In the SLT group, mean IOP at six months measured 13.33?±?2.08 mmHg with an average decrease of 30 % from preoperative IOP in the POAG group, 12.10?±?1.40 mmHg with an average decrease of 46 % in the PEX group, and 11.83?±?2.21 mmHg with an average decrease of 38 % in the PG group. In eyes without previous SLT, mean IOP sixt 6 months measured 11.00?±?1.73 mmHg with an average decrease of 38 % from preoperative IOP in the POAG group, 15.50?±?1.41 mmHg with an average decrease of 35 % in the PEX group, and 15.67?±?2.91 mmHg with an average decrease of 36 % in the PG group, respectively.

Conclusions

Prior SLT treatment seems not to negatively influence combined clear cornea phacoemulsification and Trabectome outcomes in glaucoma patients. However, SLT treatment may even have an additive effect on following combined Trabectome outcomes in patients with PEX and PG.     

d-Allose as ischemic retina injury inhibitor during rabbit vitrectomy

Purpose

To investigate the protective effects of d-allose, a rare sugar, on pressure-induced ischemia during vitrectomy in the rabbit eye.

Methods

The rabbits underwent pars plana vitrectomy, and continuous intraocular irrigation at a perfusion pressure of 140 mmHg was performed for 45 min. Intraocular pressure was regulated by adjusting the height of a bottle of balanced saline solution containing d-allose. Morphometric studies were performed to study the effects of d-allose on the histological changes induced by ischemia in the rabbit retina. Electroretinograms (ERGs) were taken before and 1 and 7 days after vitrectomy. Nitroblue tetrazolium was used as an index of superoxide anion (O ₂ ^·? ) generation. Data were analyzed by use of the unpaired Student??s t test.

Results

Seven days after ischemia, significant reductions in both number of ganglion cells and the thickness of the inner plexiform layer were observed. d-Allose significantly inhibited ischemic injury of the inner retina (P < 0.05). On postoperative day 7, amplitudes of ERG b-waves were significantly lower in the control group than in the d-allose group (P < 0.05). d-Allose suppressed the production of O₂ ^?.

Conclusions

Intraocular irrigation with d-allose during vitrectomy may protect the retina against ischemia-induced damage.     

Equivalent tamponade by room air as compared with SF6 after macular hole surgery

Background

To evaluate the effect of tamponade by room air after vitrectomy for the treatment of idiopathic macular hole (MH).

Methods

There were 156 eyes of 151 patients studied. The patients’ ages ranged from 35 to 88 years old (mean:?65.1 years). After conventional pars plana vitrectomy with internal limiting membrane peeling, fluid air exchange was performed using 20% SF₆ (Gas group: 91 eyes) or room air (Air group: 65 eyes). Surgical outcomes were retrospectively analyzed.

Results

Mean preoperative hole diameter was 352?μm in the Gas group and 370?μm in the Air group (P =?0.558). The closure rate of all cases was 91.0% after first surgery and 98.7% at last follow-up. The primary closure rate was 90.1% in the Gas group after 7.44?±?1.66 (mean ± SD) days prone positioning period, and 92.3% in the Air group after 3.83?±?0.97 days of prone positioning. There was significant difference in prone positioning period (P?<?0.0001), but not in the first closure rate (P?=?0.132).

Conclusion

This study suggests that room air may have an equivalent tamponade effect, in spite of the shorter prone positioning period, than SF₆ after MH surgery.     

Effect of vitreomacular adhesion on antivascular endothelial growth factor therapy for macular edema secondary to branch retinal vein occlusion

Purpose

To investigate the association between vitreomacular adhesion (VMA) and the visual and anatomic outcomes of antivascular endothelial growth factor therapy for macular edema due to branch retinal vein occlusion (BRVO).

Methods

This study included 107 eyes of 107 patients with BRVO who underwent intravitreal injection of 1.25 mg bevacizumab. The presence of VMA was determined with spectral-domain optical coherence tomography (SD-OCT). All eyes underwent best-corrected visual acuity (BCVA) and central retinal thickness (CRT) measurements using SD-OCT immediately before the injection and at 3, 6, 9, and 12 months after the injection. The main outcome measures were changes in BCVA and CRT from baseline.

Results

The VMA(+) and VMA(?) groups consisted of 47 and 60 eyes, respectively, and patients’ age differed significantly between the groups (P < 0.001). In both groups, BCVA and CRT improved after the injection. The VMA(+) group showed better improvement in BCVA than did the VMA(?) group (P = 0.0150), and the presence of VMA was associated with a greater decrease in CRT after adjusting for age (P = 0.0019).

Conclusions

Presence of VMA may be associated with superior visual and anatomic outcome for intravitreal bevacizumab in the treatment of macular edema due to BRVO.     

Intravitreal triamcinolone injections in non-arteritic anterior ischemic optic neuropathy

Background

In non-arteritic anterior ischemic optic neuropathy (NA-AION), no treatments have demonstrated to be effective in recovering visual loss in randomized clinical trials. Oral steroids have been evaluated, and small series of intravitreal triamcinolone acetonide (IVTA) injection in NA-AION have been reported. The purpose of our study was to report the visual outcome and morphological changes in response to a single IVTA injection as a treatment for patients with NA-AION.

Patients and methods

The charts of 36 patients with visual symptoms and optic disc swelling caused by NA-AION were evaluated. Twenty-one patients had received 4 mg IVTA and were compared with 15 non-treated patients. Visual acuity (VA), retinal nerve fiber layer thickness and static visual field were evaluated after 6 months.

Results

VA improvement at 6 months is statistically better in the treated group than in the non-treated group (p?=?0.0035). In the treated group, there was a significant inverse correlation between the delay of the injection and the visual acuity achieved at 6 months (p?<?0.0083**, r?=??0.56). A significant improvement of the visual field was noted in the injected group when compared with the non-treated group at 6 months (p?<?0.0028).

Discussion

In this retrospective study, patients receiving IVTA in the acute phase of NA-AION have better improvement of VA and visual field during the follow-up period of 6 months. However, only a large randomized controlled trial may enable to evaluate the benefits of IVTA Injections on visual outcome in NA-AION.     

Serum and aqueous humor concentrations of interleukin-27 in diabetic retinopathy patients

Purpose

Interleukin (IL)-27 has been reported to possess anti- and proinflammatory properties in several immune related-disorders, but its role in diabetic retinopathy is still elusive. Here, we aimed to (i) evaluate IL-27 concentrations in serum and aqueous humor of diabetic patients with or without retinopathy and (ii) test whether IL-27 is correlated with some risk factors of diabetic retinopathy.

Methods

The study comprised 60 diabetic patients with and without retinopathy along with 20 healthy controls. Serum and aqueous humor concentrations of IL-27 were assessed by ELISA.

Results

The mean of IL-27 concentration in aqueous humor in patients with diabetic retinopathy (6.7 ± 2.7 ng/L) was significantly elevated in comparison with either diabetic patients without retinopathy (4.6 ± 0.5 ng/L) or healthy control group (4.1 ± 0.8 ng/L). Besides, IL-27 concentration in aqueous humor was positively correlated with serum glucose, lipid profile and glycated hemoglobin (HbA1c).

Conclusions

Based on this study, IL-27 is implicated in the pathogenesis of diabetic retinopathy and positively correlates with the disorder progression.

     

The comparison of the impact of ghrelin and tacrolimus on vitreous cytokine levels in an experimental uveitis model

Background

We aimed to compare the effects of intraperitoneal ghrelin and tacrolimus on vitreous levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6) in an experimental autoimmune uveitis model.

Methods

Twenty-four male rats, each weighing 300 g, were assigned into four groups, six rats in each. All the rats, except for those in group 1, were injected intravitreally with concanavalin a to induce experimental uveitis. The development of uveitis was confirmed by the histopathologic examination of two rat globes from each group. The rats in group 2 were not given any treatment after uveitis was induced. The rats in group 3 were administered 1 mg/kg/day of intraperitoneal tacrolimus on days 0, 1, 3, 5 and 7 following the induction of uveitis (on the 14th day of study). The rats in group 4 were given 10 ng/kg/day of intraperitoneal ghrelin for 7 days following the induction of uveitis. On the 21st day of the study, all rats were sacrificed, and the eyes enucleated were subjected to histopathologic examination. Vitreous levels of TNF-α, IL-1 and IL-6 were measured by the enzyme-linked immunosorbent assay method.

Results

The histopathologic evaluation carried out to confirm the development of uveitis revealed destruction in the retinae and ciliary bodies of the immunized rats. The mean vitreous levels of TNF-α, IL-1 and IL-6 were significantly higher in the sham group than in the control group (p?<?0.05). The levels of these three cytokines showed a significant decrease in the tacrolimus treatment group (p?<?0.05). Cytokine levels decreased in the ghrelin treatment group relative to the control group; however, the decrease was not found statistically significant (p?>?0.05).

Conclusions

Tacrolimus could be effective in uveitis treatment by neutralizing or decreasing the levels of cytokines such as TNF-α, IL-1 and IL-6 that have a critical part in the pathogenesis of uveitis. However, ghrelin failed to produce the desired effect. Further studies using different doses and different ways of administration are needed to determine the effective dose of ghrelin in uveitis.     

Visual outcome of photodynamic therapy for typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy over 5 years of follow-up

Purpose

To evaluate the long-term effects of photodynamic therapy (PDT) on typical neovascular age-related macular degeneration (tAMD) and polypoidal choroidal vasculopathy (PCV).

Methods

This was a multicenter prospective study of 139 eyes from 136 patients (tAMD: 74 eyes; PCV: 65 eyes) who underwent PDT as the initial treatment. The change in best-corrected visual acuity (BCVA), predictive factors for the BCVA at 60 months, frequency of recurrence, and mean recurrence period were analyzed.

Results

The pre-PDT BCVA and greatest linear dimension (GLD) did not differ between the two groups. The mean BCVA (logMAR) was significantly improved at 6 months post-initial PDT (post-PDT) in the PCV group (?0.11, P = 0.0091). However, at 60 months post-PDT, the mean BCVA was significantly worse than baseline in the tAMD (+0.21, P = 0.0035) and PCV (+0.21, P = 0.0076) groups. Pre-PDT BCVA, age, and GLD were the factors significantly associated with the BCVA at 60 months post-PDT. Although the frequency of recurrence did not significantly differ between the two phenotype groups, the mean recurrence period was significantly longer in the PCV group than in the tAMD group (15.7 vs. 8.6 months, P = 0.0020).

Conclusions

PDT may not have benefits for visual acuity in cases of tAMD and PCV over 5 years of follow-up.     

Quadrantal macular retinal thickness changes in strabismus subjects with abnormal binocular vision development

Purpose

To investigate retinal morphological changes in strabismus patients with abnormal binocular vision development by comparing differences in quadrantal macular retinal thickness.

Methods

Six strabismus patients (6 dominant and 5 non-dominant eyes) with abnormal binocular vision (mean age 22 years), and 11 control subjects (11 dominant and 11 non-dominant eyes) (mean age 21 years) were enrolled. Macular retinal thickness measurements were performed by optical coherence tomography, with total macular retinal (TMR) and ganglion cell complex (GCC) thicknesses measured in 3- and 6-mm regions in each quadrant. Measurement values were then used to determine quadrant ratios.

Results

Compared to the dominant eyes of the controls, the superior/inferior (S/I) ratio of the TMR thickness and GCC thickness in the 3-mm region was significantly lower in the dominant eyes of the strabismus group (P < 0.05, each). The superior temporal/inferior temporal (ST/IT) ratio of the GCC thickness in the dominant eyes of the strabismus group was also significantly lower (P < 0.01).

Conclusions

Dominant eyes of the strabismus group with abnormal binocular vision development exhibited thinner superior temporal GCC thicknesses in the 3-mm region. Retinal ganglion cells in this region might be affected by efferent neural degeneration that originates in the visual pathway responsible for adaptations to the visual experience.     

Anti-angiogenic effect of KH902 on retinal neovascularization

Purpose

KH902 is a fusion protein derived from the extracellular domains of vascular endothelial growth factor (VEGF) receptors 1 and 2 and the Fc portion of immunoglobulin G1 (IgG1). Retinopathy of prematurity (ROP) is an eye disease that affects premature babies who have received intensive neonatal care, and the disorganization of retinal blood vessels may result in scarring and retinal detachment. This study was designed to examine the inhibitory effects of KH902 on mice with oxygen-induced retinopathy (OIR), one of the animal models of ROP.

Methods

Human umbilical vein endothelial cells (HUVECs) were used for an in vitro study, and the C57BL/6 J OIR mouse model was used for an in vivo study. HUVECs were incubated with KH902 or a VEGF- and KH902-containing medium. Cell proliferation, migration, apoptosis, and tube formation were measured with BrdU incorporation, Transwell, flow cytometry, and Matrigel assays. C57BL/6 J mice were exposed to 75 % oxygen from postnatal day 7 (P7) to P12, after which the mice were brought to room air and intravitreously injected with KH902. At P18, the mice were perfused with fluorescein isothiocyanate (FITC)-dextran and Evans Blue, and flat-mounted retinas were used to measure the non-perfused and leakage areas. The data were analyzed with GraphPad Prism 5.0 software.

Results

In vitro, KH902 dose-dependently inhibited HUVEC proliferation in general culture medium and in VEGF₁₆₅-containing medium at different time points. Moreover, KH902 inhibited HUVEC migration and tube formation and induced HUVEC apoptosis. In vivo, an intravitreous injection of KH902 reduced the retinal non-perfused area from 34 % in the control group to 19 % in the treatment group and significantly reduced the retinal leakage area from 18 % to 9 %.

Conclusion

KH902 had marked inhibitory effects on angiogenesis both in vitro and in vivo. These data suggest that KH902 could serve as an innovative pharmaceutical agent to prevent retinal neovascularization (NV) and as a strategy for the treatment of ROP.     

A prevalence study of IgG4-related ophthalmic disease in Japan

Purpose

Immunoglobulin (Ig)G4-related ophthalmic disease belongs to a category of ocular adnexal lymphoproliferative disorders, the most frequent group of orbital tumors and simulating lesions. The aim of this study was to elucidate the number of IgG4-related diseases of orbital lymphoproliferative disorders and correlate ages and sex of such patients from 18 centers in Japan.

Methods

One thousand and fourteen patients with orbital lymphoproliferative disorders were enrolled in this study. All had pathologically diagnosed lymphoproliferative disorders with surgical samples of ocular adnexal tissue. Patients with conjunctival lesions and intraocular lymphoma were excluded.

Results

Of the 1,014 cases of orbital lymphoproliferative disorders 404 (39.8 %) had extranodal mucosa-associated lymphoid tissue (MALT) lymphoma, 156 (15.4 %) had other malignant lymphomas, 191 (18.8 %) had non-IgG4 orbital inflammation, 219 (21.6 %) had IgG4-related orbital inflammation, and 44 (4.3 %) had IgG4-positive MALT lymphoma. Median age of the IgG4-related orbital inflammation group was 62 years, which is significantly lower than that of the MALT lymphoma group (median 66 years) and higher than the non-IgG4 orbital inflammation group (median 57 years). The male/female ratio was 105/114 in the IgG4-related orbital inflammation group.

Conclusions

Nearly a quarter of orbital lymphoproliferative disorders in Japan are related to IgG4.     

Long-term results of treatment with diquafosol ophthalmic solution for aqueous-deficient dry eye

Purpose

To evaluate the preliminary long-term efficacy of diquafosol ophthalmic solution for aqueous-deficient dry eye.

Methods

Fifteen patients with mild-to-moderate aqueous-deficient dry eye were enrolled. After a washout period, the patients were treated with 3 % diquafosol ophthalmic solution for 6 months. We assessed 12 subjective dry eye symptoms, corneal and conjunctival staining with fluorescein, tear film break-up time (BUT), lower tear meniscus height measured with anterior-segment optical coherence tomography, Schirmer’s testing, and adverse reactions at baseline and 1, 3, and 6 months after the start of treatment.

Results

Treatment with diquafosol ophthalmic solution significantly improved dry eye symptoms, corneal staining, BUT, and tear meniscus height at 1 month and maintained the effectiveness for 6 months. Conjunctival staining significantly improved 3 and 6 months after treatment. No significant adverse reactions developed.

Conclusions

Prolonged use of diquafosol ophthalmic solution for 6 months produced significant improvement both subjectively (dry eye symptom score) and objectively (ocular staining score and tear function tests) for aqueous-deficient dry eye.     

Tenon advancement and duplication technique to prevent postoperative Ahmed valve tube exposure in patients with refractory glaucoma

Purpose

To present and compare the long-term results of Dr. Tamcelik’s previously described technique of Tenon advancement and duplication with the conventional Ahmed glaucoma valve (AGV) implantation technique in patients with refractory glaucoma.

Methods

This study was a multicenter, retrospective case series that included 303 eyes of 276 patients with refractory glaucoma who underwent glaucoma valve implantation surgery. The patients were divided into three groups according to the surgical technique applied and the outcomes compared. In group 1, 96 eyes of 86 patients underwent AGV implant surgery without patch graft; in group 2, 78 eyes of 72 patients underwent AGV implant surgery with donor scleral patch; in group 3, 129 eyes of 118 patients underwent Ahmed valve implant surgery with “combined short scleral tunnel with Tenon advancement and duplication technique”. The endpoint assessed was tube exposure through the conjunctiva.

Results

In group 1, conjunctival tube exposure was seen in 11 eyes (12.9 %) after a mean 9.2 ± 3.7 years of follow-up. In group 2, conjunctival tube exposure was seen in six eyes (2.2 %) after a mean 8.9 ± 3.3 years of follow-up. In group 3, there was no conjunctival exposure after a mean 7.8 ± 2.8 years of follow-up. The difference between the groups was statistically significant. (P = 0.0001, Chi-square test).

Conclusion

This novel surgical technique combining a short scleral tunnel with Tenon advancement and duplication was found to be effective and safe to prevent conjunctival tube exposure after AGV implantation surgery in patients with refractory glaucoma.