Pars plana vitrectomy and scleral-fixated intraocular lenses: comparison of Gore-Tex suture and flanged intrascleral haptic fixation techniques.

OBJECTIVE: To compare clinical outcomes of combined pars plana vitrectomy (PPV) and secondary scleral fixation of an intraocular lens (IOL) using Gore-Tex suture versus flanged intrascleral haptic fixation (FIHF) using double needles. DESIGN: Single-centre retrospective cohort series. PARTICIPANTS: Eyes undergoing PPV with simultaneous scleral fixation of an IOL. METHOD: Eyes that underwent fixation of a Bausch & Lomb Akreos AO60 or enVista MX60E IOL using Gore-Tex suture or a Tecnis ZA9003 or Zeiss CT LUCIA 602 IOL using FIHF were included. The primary outcome was change from baseline visual acuity to postoperative month 3. Secondary outcomes included deviation from refractive target aim and rates of postoperative complications. RESULTS: Seventy-nine eyes of 72 patients were included. Mean (±SD) follow-up was 16 ± 10.5 months (range, 4.5-45.2 months). Fifty-three eyes (67.1%) underwent Gore-Tex suture fixation, and 26 eyes (32.9%) underwent FIHF. Across all eyes, mean visual acuity improved from 1.30 ± 0.74 logMAR (20/399 Snellen equivalent) preoperatively to 0.36 ± 0.36 logMAR (20/45 Snellen equivalent) at 3 months (p < 0.001). No difference in visual acuity at month 3 was noted between the 2 techniques (p = 0.34). Mean deviation from refractive target aim was not significantly different between the Gore-Tex and FIHF groups (+0.14 ± 1.33 D vs -0.16 ± 0.88 D; p = 0.45). Reoperation rates were similar between groups (2 of 53 eyes in the Gore-Tex group vs 3 of 26 eyes in the FIHF group; p = 0.32). CONCLUSION: Combined PPV and scleral fixation of IOLs with Gore-Tex suture and FIHF resulted in similar improvements in visual acuity. No significant differences in refractive outcome and postoperative complication profiles were noted.

Retained lens fragment presenting 32 years after cataract extraction.

Purpose: To report a patient with retained lens material presenting over three decades after initial cataract extraction with fluctuating corneal edema and intraocular inflammation. Observations: A 66-year-old man presented with a first episode of decreased vision and photophobia 32 years after cataract extraction without intraocular lens implantation in the right eye. Slit lamp examination revealed a tan-colored oblong mass in the inferior angle, in addition to corneal edema and an anterior chamber reaction. The patient was aphakic with traumatic mydriasis, and accordingly it was noted that the mass shifted location between anterior and posterior chambers over subsequent evaluations. The anterior chamber inflammation resolved in the latter position. The patient was requested to remain prone prior to clinical evaluation, and an in-office anterior chamber aspiration was performed. Histopathologic evaluation confirmed the presence of lens material and a phacolytic response. Conclusions And importance: Although unusual, retained lens material may manifest with ocular morbidity decades after cataract extraction. In patients with corneal edema and intraocular inflammation, retained lens material should be considered as a possible underlying cause even in patients with a remote history of cataract extraction. This case represents one of the longest reported time periods from cataract extraction to clinical presentation of retained lens material.

Predictors of Lost to Follow-Up in Patients Being Treated for Proliferative Diabetic Retinopathy.

PURPOSE: To identify risk factors for patients with proliferative diabetic retinopathy (PDR) who are lost to follow-up (LTFU) while undergoing intravitreal injections of anti-VEGF (IVIs) and/or panretinal photocoagulation (PRP) at an urban institution. DESIGN: Retrospective cohort study. METHODS: A chart review was performed in a total of 418 adult patients with PDR who received IVI and/or PRP between January 1, 2014, and June 1, 2018, at the authors' institution. Rates of LTFU, risk factors associated with LTFU, and vision outcomes were assessed. RESULTS: Of a total of 418 patients, 256 patients (61%) were LTFU. Risk factors positively associated with LTFU on multivariate analysis included non-English as the primary language (odds ratio [OR], 1.83; P = .006); age 56-65 years old (OR, 1.86; P = .014); age older than 65 years (OR, 1.94; P = .027) compared to age 55 years or younger; living 20 miles or less from the institution (OR, 2.68; P = .009); having greater than 5 comorbidities (OR, 2.38; P = .034); seeing 20 or more distinct departments (OR, 4.66; P = .007); missing more than 10% of non-eye care appointments (OR, 1.61; P = .038); and receiving only PRP compared to only IVIs (OR, 1.93; P = .031). CONCLUSIONS: A high percentage of patients treated for PDR at the authors' institution were LTFU over a 4-year time span. Identifying patients at high risk for being LTFU may help in choosing treatment modality and appropriate patient counseling.

High Glucose Induces Mitochondrial Dysfunction in Retinal Müller Cells: Implications for Diabetic Retinopathy.

Purpose: To investigate whether high glucose (HG) induces mitochondrial dysfunction and promotes apoptosis in retinal Müller cells. Methods: Rat retinal Müller cells (rMC-1) grown in normal (N) or HG (30 mM glucose) medium for 7 days were subjected to MitoTracker Red staining to identify the mitochondrial network. Digital images of mitochondria were captured in live cells under confocal microscopy and analyzed for mitochondrial morphology changes based on form factor (FF) and aspect ratio (AR) values. Mitochondrial metabolic function was assessed by measuring oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) using a bioenergetic analyzer. Cells undergoing apoptosis were identified by differential dye staining and TUNEL assay, and cytochrome c levels were assessed by Western blot analysis. Results: Cells grown in HG exhibited significantly increased mitochondrial fragmentation compared to those grown in N medium (FF = 1.7 ± 0.1 vs. 2.3 ± 0.1; AR = 2.1 ± 0.1 vs. 2.5 ± 0.2; P < 0.01). OCR and ECAR were significantly reduced in cells grown in HG medium compared to those grown in N medium (steady state: 75% ± 20% of control, P < 0.02; 64% ± 22% of control, P < 0.02, respectively). These cells also exhibited a significant increase (∼2-fold) in the number of apoptotic cells compared to those grown in N medium (P < 0.01), with a concomitant increase in cytochrome c levels (247% ± 94% of control, P < 0.05). Conclusions: Findings indicate that HG-induced mitochondrial morphology changes and subsequent mitochondrial dysfunction may contribute to retinal Müller cell loss associated with diabetic retinopathy.

Association of reduced Connexin 43 expression with retinal vascular lesions in human diabetic retinopathy.

Connexin 43 (Cx43) downregulation promotes apoptosis in retinal vascular cells of diabetic animal models; however, its relevance to human diabetic retinopathy has not been established. In this study, we investigated whether diabetes alters Cx43 expression and promotes retinal vascular lesions in human retinas. Diabetic human eyes (aged 64-94 years) and non-diabetic human eyes (aged 61-90 years) were analyzed in this study. Retinal protein samples and retinal capillary networks were assessed for Cx43 level by Western blot (WB) analysis and immunostaining. In parallel, retinal capillary networks were stained with hematoxylin and periodic acid Schiff to determine the extent of pericyte loss (PL) and acellular capillaries (AC) in these retinas. Cx43 protein expression was significantly reduced in the diabetic retinas compared to non-diabetic retinas as indicated by WB analysis (81 ± 11% of control). Additionally, a significant decrease in the number of Cx43 plaques per unit length of vessel was observed in the diabetic retinas compared to those of non-diabetic retinas (62 ± 10% of control; p < 0.005). Importantly, a strong inverse relationship was noted between Cx43 expression and the relative number of AC (r = -0.89; p < 0.0005), and between Cx43 expression and number of pericyte loss (r = -0.88; p < 0.0005). Overall, these results show that Cx43 expression is reduced in the human diabetic retinas and Cx43 reduction is associated with increased vascular cell death. These findings suggest that diabetes decreases retinal Cx43 expression and that the development of PL and AC is associated with reduced Cx43 expression in human diabetic retinopathy.

Downregulation of Connexin 43 promotes vascular cell loss and excess permeability associated with the development of vascular lesions in the diabetic retina.

PURPOSE: To determine whether downregulation of Connexin 43 (Cx43) expression promotes development of acellular capillaries (ACs), pericyte loss (PL), excess permeability, and retinal thickening in rat retinas. METHODS: Control rats, diabetic rats, and rats intravitreally injected with Cx43 siRNA or scrambled siRNA were used in this study to determine if acute downregulation of Cx43 expression contributes to retinal vascular cell death and excess permeability. Western blot (WB) analysis and Cx43 immunostaining were performed to assess Cx43 protein levels and distribution in the retinal vessels. Concurrently, retinal networks were subjected to terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling (TUNEL) assay and counter-stained to assess the number of apoptotic cells, ACs, and PL. Assessment of fluorescein isothiocyanate-dextran (FITC-dex) extravasation from retinal capillaries and optical coherence tomography (OCT) were performed to determine retinal vascular permeability and retinal thickness, respectively. RESULTS: WB analysis indicated a significant decrease in the Cx43 protein level in the retinas of the diabetic rats and those intravitreally injected with Cx43 siRNA compared to the retinas of the control rats. Likewise, the retinal vascular cells of the diabetic rats and the Cx43 siRNA-treated rats showed a significant decrease in Cx43 immunostaining. Importantly, the number of apoptotic cells, ACs and PL, FITC-dex extravasation, and thickness increased in the retinas of the diabetic and Cx43 siRNA-treated rats compared to those of the control rats. CONCLUSIONS: Results indicate that downregulation of Cx43 expression alone induces vascular cell death and promotes vascular permeability in the retina. These findings suggest that diabetes-induced downregulation of Cx43 participates in promoting retinal vascular lesions associated with diabetic retinopathy (DR).

High glucose alters Cx43 expression and gap junction intercellular communication in retinal Müller cells: promotes Müller cell and pericyte apoptosis.

PURPOSE: To investigate whether high glucose (HG) alters connexin 43 (Cx43) expression and gap junction intercellular communication (GJIC) activity in retinal Müller cells, and promotes Müller cell and pericyte loss. METHODS: Retinal Müller cells (rMC-1) and cocultures of rMC-1 and retinal pericytes were grown in normal (N) or HG (30 mM glucose) medium. Additionally, rMC-1 transfected with Cx43 small interfering RNA (siRNA) were grown as cocultures with pericytes, and rMC-1 transfected with Cx43 plasmid were grown in HG. Expression of Cx43 was determined by Western blotting and immunostaining and GJIC was assessed by scrape-loading dye transfer (SLDT) technique. Apoptosis was analyzed by TUNEL or differential staining assay, and Akt activation by assessing Akt phosphorylation. RESULTS: In monocultures of rMC-1 and cocultures of rMC-1 and pericytes, Cx43 protein level, number of Cx43 plaques, GJIC, and Akt phosphorylation were significantly reduced in HG medium. Number of TUNEL-positive cells was also significantly increased in rMC-1 monocultures and in rMC-1 and pericyte cocultures grown in HG medium. Importantly, when rMC-1 transfected with Cx43 siRNA were grown as cocultures with pericytes, a significant decrease in GJIC, and increase in TUNEL-positive cells was observed, concomitant with decreased Akt phosphorylation. Upregulation of Cx43 rescued rMC-1 from HG-induced apoptosis. CONCLUSIONS: Gap junction communication between Müller cells and pericytes is essential for their survival. Downregulation of Cx43 that is HG induced and impairment of GJIC activity in Müller cells contributes to loss of glial and vascular cells associated with the pathogenesis of diabetic retinopathy.

Effects of high glucose-induced Cx43 downregulation on occludin and ZO-1 expression and tight junction barrier function in retinal endothelial cells.

PURPOSE: To investigate whether high glucose (HG)-induced downregulation of connexin 43 (Cx43), a gap junction protein, alters ZO-1 and occludin expression and cell monolayer permeability. METHODS: Rat retinal endothelial cells (RRECs) were grown in normal (N; 5 mM) medium, high glucose (HG; 30 mM) medium, N medium transfected with Cx43 siRNA, or N medium transfected with scrambled siRNA. To determine Cx43, occludin, and ZO-1 protein expression, Western blot (WB) analysis and immunostaining were performed. Gap junction intercellular communication (GJIC) was determined using scrape load dye transfer (SLDT) assay. In parallel, cell monolayer permeability was assessed in the four groups of cells, and in cells transfected with Cx43 plasmid or dominant negative Cx43 plasmid. RESULTS: Connexin 43 protein expression was significantly reduced in cells grown in HG (67 ± 15% of control), and a significant reduction in Cx43 was achieved when cells grown in N medium were transfected with Cx43 siRNA (76 ± 12% of control), with concomitant decrease in GJIC activity. Cells grown in HG showed significant reduction in occludin (77 ± 9% of control) and ZO-1 (80 ± 11% of control) protein level compared with cells grown in N media. Importantly, cells transfected with Cx43 siRNA and grown in N medium showed significant downregulation in occludin (78 ± 8% of control) and ZO-1 (81 ± 6% of control) expression, and exhibited increased cell monolayer permeability. Furthermore, Cx43 upregulation protected cells against HG-induced excess cell monolayer permeability. CONCLUSIONS: Our findings indicate that HG-induced downregulation of Cx43 expression and GJIC may contribute to the breakdown of endothelial barrier tight junctions associated with diabetic retinopathy.

High glucose-induced downregulation of connexin 30.2 promotes retinal vascular lesions: implications for diabetic retinopathy.

PURPOSE: To investigate whether high glucose (HG) alters expression of connexin 30.2 (Cx30.2) and influences gap junction intercellular communication (GJIC) in retinal endothelial cells and promotes vascular lesions characteristic of diabetic retinopathy (DR). METHODS: Western blot analysis and immunostaining were performed to determine Cx30.2 protein expression and localization in rat retinal endothelial cells (RRECs) grown in normal (N; 5 mM) or HG (30 mM) medium for 7 days. Concurrently, GJIC was assessed in cells grown in N or HG medium and in cells transfected with Cx30.2 siRNA. Similarly, retinal Cx30.2 expression was assessed in nondiabetic and diabetic rats. Additionally, the effect of reduced Cx30.2 on development of acellular capillaries (ACs) and pericyte loss (PL) was studied in retinas of Cx30.2 knockout mice. RESULTS: Cx30.2 was identified in RRECs in vitro and in vascular cells of retinal capillaries. RRECs grown in HG exhibited significantly reduced Cx30.2 protein levels consistent with decreased Cx30.2 immunostaining compared with those grown in N medium. Cells grown in HG and cells transfected with Cx30.2 siRNA exhibited significantly diminished dye transfer compared with N or nontransfected cells. Importantly, Cx30.2 protein level and immunostaining were decreased in diabetic retinas compared with nondiabetic retinas. Retinal capillaries of Cx30.2 knockout mice exhibited increased numbers of ACs and PL compared with those of wild-type mice. CONCLUSIONS: These results indicate that HG- or diabetes-induced downregulation of Cx30.2 expression and decrease in GJIC activity play a critical role in the development of retinal vascular lesions in early DR.

Mitochondrial dysfunction and endoplasmic reticulum stress in diabetic retinopathy: mechanistic insights into high glucose-induced retinal cell death.

Hyperglycemia, a prominent characteristic of diabetes, has been implicated in the apoptotic death of vascular and neuronal cells in the retina. In diabetic retinopathy, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and subsequent breakdown of cellular homeostasis play a critical role in retinal cell death. In particular, changes in mitochondrial morphology, mitochondrial membrane potential heterogeneity, oxygen consumption rate and protein misfolding are beginning to be recognized as key players in the demise of retinal vascular cells in diabetes. Some of these key changes contribute to oxidative stress and influence ion transport, impacting overall cellular homeostasis. The primary objective of this review is to provide insight into the mechanisms in which high glucose influences two disparate cellular organelles, mitochondria and ER, in promoting apoptotic demise of retinal vascular and neuronal cells in diabetic retinopathy.

Case of bilateral complete posterior dislocation of lens caused by elder abuse.

We report a case of bilateral complete dislocation of lenses into the vitreous cavities due to elder abuse in a patient with senile dementia. According to the patient's son, bilateral complete lens dislocation occurred after he hit his father in the head with socks in order to control his violent behavior. Although the patient was taken to our ophthalmological ward for a planned vitrectomy, restlessness and inability to remain in his room during the night led to his leaving the hospital. The patient has not returned but did receive a vitrectomy at another clinic. While the number of patients with senile dementia has dramatically increased, no specific remedy is currently available. When treating medical concerns of seniors with unknown backgrounds, elder abuse needs to be considered as a potential cause of such injuries.