Pascal short-pulse plus subthreshold endpoint management laser therapy for diabetic macular edema: the "sandwich technique".

BACKGROUND: Diabetic macular edema (DME) is the main cause of visual loss in diabetic patients. Despite the use of anti-VEGF therapy as first-line treatment, there are many patients whose response to treatment is poor or transient at best. Sophisticated laser techniques have emerged aiming at low-intensity retinal damage, avoiding excessive heat that causes tissue necrosis and related collateral effects. OBJECTIVE: To evaluate the effect of combined sublethal laser modalities from short-pulse duration (SPD) with endpoint management (EpM) subthreshold laser [named the "sandwich technique" (SWiT)] on central subfield thickness (CST) and best-corrected visual acuity (BCVA) in patients with DME. MATERIAL AND METHODS: In this consecutive retrospective study, 37 patients (37 eyes) with center-involved (CI) DME were treated with SWiT laser therapy from April 2017 to June 2021. The technique consisted of a mean number of 200 (range number 50-400) SPD laser burns OCT-guided thickened area performed on the juxta- and perifoveal area 500 µm away from the foveal center, overlapping with a mean number of 1000 (range number 800-1200) EpM laser burns focused on 6 mm macular diameter area but saving 300 µm toward the foveal center. All patients underwent ophthalmological evaluations, including BCVA and CST measurement by spectral-domain optical coherence tomography (SD-OCT), before and after SWiT laser therapy. The mean follow-up time was 19.2 months (range 2-60 months). RESULTS: Thirty-five out of 37 cases showed an improvement in CST and BCVA following treatment. At baseline, mean CST (µm) ± standard error (SE) and mean BCVA (logMAR) ± SE was 456.95 ± 37.00 and 0.71 ± 0.29, respectively. After a mean follow-up of 19.2 months, mean CST (µm) ± SE and BCVA (logMAR) ± SE were 272.09 ± 9.10 (p < 0.0001) and 0.54 ± 0.26 (p = 0.003), respectively. A statistically significant reduction in CST and improvement in BCVA was noted after laser therapy application. The anti-VEGF injection frequency was reduced during the mean 19.2 months of the study period. CONCLUSIONS: The novel "sandwich" laser therapy aid reduced CST and improved BCVA in this retrospective case series. Further prospective studies are warranted.

Experimental selective choriocapillaris photothrombosis using a modified indocyanine green formulation.

BACKGROUND: This in vivo study assessed and compared the effectiveness of an aqueous indocyanine green (ICG) formulation (R-ICG) and a lipid ICG formulation (L-ICG) in occluding the rabbit choriocapillaris, and determined the singlet oxygen quantum yields and aggregation properties of both formulations in vitro. METHODS: Singlet oxygen production and aggregation were compared. The eye fundus of 30 albino rabbits was irradiated 0-15 min after dye injection using an 810 nm diode laser. Fluorescein angiography and light microscopy were used to evaluate the safety and efficacy of R-ICG and L-ICG. RESULTS: L-ICG decreased the dimerisation constant and the tendency of ICG to form aggregates, and increased the efficiency of ICG in generating singlet oxygen (R-ICG, PhiDelta = 0.120 and L-ICG, PhiDelta = 0.210). Using a 10 mg/kg dose, choriocapillaris occlusion was achieved at a light dose of 35.8 J/cm(2) with L-ICG and 71.6 J/cm(2) with R-ICG with minimal damage to the neurosensory retina. CONCLUSION: Restrictions to the use of ICG in aqueous solution, low singlet oxygen quantum yields and high aggregation tendency, were overcome with L-ICG. The lower laser irradiance required to obtain choriocapillaris occlusion may suggest that L-ICG is a more potent and selective photosensitiser than R-ICG.

Retinal nerve fibre layer thickness profile in normal eyes using third-generation optical coherence tomography.

AIMS: To establish four normal retinal nerve fibre layer (RNFL) thickness radial profiles based on third-generation optical coherence tomography (OCT) and to compare them with previously reported histologic measurements. METHODS: A total of 20 normal eyes were studied. A circular scan was adjusted to the size of the optic disc and three scans were performed with this radius and every 200 microm thereafter, up to a distance of 1400 microm. Four different radial sections (superotemporal, superonasal, inferonasal, and inferotemporal) were studied to establish RNFL thickness OCT profiles. Additionally, two radial scans orientated at 45 and 135 degrees crossing the optic disc centre were performed in six of 20 eyes, and RNFL thickness was measured at disc margin. RESULTS: Quadrant location and distance from disc margin interaction in RNFL thickness was statistically significant (P<0.001). The RNFL thickness decreased (P<0.001) as the distance from the disc margin increased for all sections. The measurements automatically generated by the OCT built-in software were thinner (P<0.001) than histologic ones close to the disc margin. CONCLUSIONS: Four normal OCT RNFL profiles were established and compared with histological data obtained from the same area. RNFL measurements assessed by OCT 3 were significantly thinner close to the optic disc margin.

An intravitreal biodegradable sustained release naproxen and 5-fluorouracil system for the treatment of experimental post-traumatic proliferative vitreoretinopathy.

BACKGROUND/AIMS: To determine the potential of an intravitreal sustained release naproxen and 5-fluorouracil (NA/5-FU) codrug for the treatment of experimental proliferative vitreoretinopathy (PVR) in a model for trauma associated tractional retinal detachment (TRD). METHODS: Sustained release pellets were prepared by covalently linking naproxen to 5-fluorouracil. Drug release was tested in vitro and toxic effects were evaluated by electroretinography and light microscopy. Traumatic PVR was induced in pigmented rabbits by performing a scleral laceration, followed by repair and intravitreal injection of 0.4 ml of autologous blood. Thirty six eyes were treated with a sustained release implant containing 1.5 mg NA/5-FU as a codrug and 36 control eyes were submitted to surgery alone. Eyes were evaluated for TRD by serial indirect ophthalmoscope examination at different time points followed by postmortem fundus evaluation of the enucleated eye RESULTS: The NA/5-FU pellets were found to provide linear release of 5-FU and naproxen over the 30 day duration of the in vitro release test. Both the severity of PVR grade and the percentage of eyes with moderate or worse tractional detachment were significantly lower in eyes treated with the codrug pellet. There were no drug related toxic effects evident on histopathological or electroretinograph examination of eyes containing the NA/5-FU pellet. CONCLUSIONS: The results suggest that this NA/5-FU codrug device effectively inhibits the progression of PVR in a rabbit trauma model that closely resembles PVR in humans. Additional studies to add knowledge to these initial findings and to clarify the potential of the codrug device for the treatment of human PVR are warranted.

Indocyanine green mediated photothrombosis for the management of predominantly classic choroidal neovascularisation caused by age related macular degeneration.

AIMS: To study the effectiveness of indocyanine green mediated photothrombosis in the management of predominantly classic subfoveal choroidal neovascularisation associated with age related macular degeneration. METHODS: Prospective, non-comparative, interventional case series of nine patients with predominantly classic subfoveal choroidal neovascularisation secondary to age related macular degeneration who declined photocoagulation or verteporfin photodynamic therapy. Patients were submitted to one or more treatments with an intravenous injection of a small volume of high concentration indocyanine green solution followed by low irradiance, large spot 810 nm continuous laser application via a transpupillary approach. Main outcome measures were change in best corrected visual acuity and macular exudative manifestations. RESULTS: After 12 months of follow up, the final best corrected visual acuity was the same (plus or minus two ETDRS lines) in five eyes (55%), improved more than two ETDRS lines in three eyes (33%), and worsened by more than two lines in the remaining eye. The improved vision was probably related to partial or complete restoration of the macular architecture as a result of fluid resolution, whereas the worsened vision was primarily the result of treatment failure in achieving substantial choroidal neovascular occlusion. There were no complications related to the procedure. CONCLUSION: Indocyanine green mediated photothrombosis may be an effective alternative treatment for predominantly classic subfoveal choroidal neovascularisation caused by age related macular degeneration.

Indocyanine green-mediated photothrombosis combined with intravitreal triamcinolone for the treatment of choroidal neovascularization in serpiginous choroiditis.

PURPOSE: To report a case of peripapillary choroidal neovascularization (CNV) complicating serpiginous choroiditis that was treated by a single indocyanine green (ICG)-mediated photothrombosis session combined to intravitreous triamcinolone acetonide (TA) injection. METHODS: Interventional case report. A 48-year-old patient with peripapillary CNV was submitted to a laser-dye-mediated technique that uses ICG and low-intensity 810-nm light for continuous laser application; TA was then injected into the vitreous cavity 1 hour later, and prospective evaluation with fluorescein and ICG angiography as well as optical coherence tomography (OCT) was performed. RESULTS: At 2 weeks after treatment, best-corrected visual acuity improved from 20/200 to 20/50, with further improvement to 20/20-1 in the subsequent 10 weeks. Absence of fluorescein leakage from the CNV and OCT evidence of resolved retinal oedema was observed at that time. Clinical stabilization was maintained up to 1 year of follow-up. There was no significant complication related to the procedure. CONCLUSION: Combined ICG-mediated photothrombosis and intravitreous TA induced rapid and significant visual acuity recovery in this particular case of peripapillary CNV complicating serpiginous choroiditis. Accordingly, angiographic and OCT findings demonstrated neovascular lesion regression and restoration of the macular architecture.

Diode laser modifications for treatment of choroidal neovascularisation.

The aim of this paper is to describe various diode laser modifications and their use in treating choroidal neovascularisation in age-related macular degeneration. Diode lasers are used to treat selected choroidal neovascular membranes. Alterations in microprocessor connectivity, and parameters such as maximum spot size, light delivery time and coupled Joule meter, were made so that ophthalmic surgeons could specify treatment possibilities. A trimodal (photocoagulation, transpupillary thermotherapy and photodynamic therapy) application laser device coupled to a single light source has been developed. The new diode laser modifications were technically successful. Microprocessor connectivity was obtained, larger spot sizes were achieved, light delivery time could be extended and energy parameters were available at the display.

Optical coherence tomography in choroidal neovascular membrane associated with Best's vitelliform dystrophy.

A 29-year-old black male with Best's dystrophy presented an elevated choroidal neovascular membrane in the right eye that was diagnosed and followed with fluorescein-indocyanine green angiography and optical coherence tomography. The subretinal neovascularization was successfully treated with argon laser photocoagulation. One month later, the visual acuity improved and an optical coherence tomography confirmed regression of the serous macular detachment. The final clinical picture remained stable for 12 months of follow-up.

Choriocapillaris photodynamic therapy using indocyanine green.

PURPOSE: To evaluate the potential of photodynamic therapy using indocyanine green for occlusion of choroidal neovascularization, the authors studied efficiency and collateral damage of photodynamic therapy-induced photothrombosis in the rabbit choriocapillary layer. METHODS: Fundus photography, fluorescein angiography, and light and transmission electron microscopy were used to study the efficiency of photodynamic therapy-induced photothrombosis using indocyanine green as the photosensitizer, and to assess the resultant collateral damage. The delivery system consisted of a modified infrared diode laser tuned to 810 nm, near the maximum absorption peak of indocyanine green. RESULTS: Choriocapillary occlusion was achieved at indocyanine green doses of 10 and 20 mg/kg and a radiant as low as 6.3 J/cm(2). When photodynamic therapy was performed with indocyanine green doses of 10 mg/kg, damage to the neural retina was minimal. Only inner photoreceptor segments showed degeneration, probably secondary to choroidal ischemia. Bruch membrane remained intact. Retinal pigment epithelium was invariably damaged, as seen with other photosensitizers. Temporary occlusion of large choroidal vessels occurred at both dye doses. CONCLUSIONS: In this experimental study, photodynamic therapy using indocyanine green and 810-nm light irradiation produced endothelium-bound intraluminal photothrombosis, with preservation of the retinal architecture and minimal loss of visual cells. Membrane targetability, hydrophilic and fluorescent properties, and activation at 805 nm suggest indocyanine green as a potential photosensitizer for choroidal neovascularization. These combined considerations point toward further study of photodynamic therapy using indocyanine green for the treatment of choroidal vascular disease.

Optical coherence tomography evaluation of idiopathic macular hole treatment by gas-assisted posterior vitreous detachment.

PURPOSE: To report a case of idiopathic macular hole, with vitreoretinal traction confirmed by optical coherence tomography that was successfully treated by a single intravitreous perfluoropropane (C(3)F(8)) gas bubble injection. METHODS: Case report. A 65-year-old patient with idiopathic macular hole (stage 2, one eye) received an intravitreous gas injection and was prospectively followed with optical coherence tomography. RESULTS: A complete posterior vitreous detachment was achieved within 6 weeks after gas injection. Visual acuity improved from 20/80 to 20/25 by 10 months of follow-up. Optical coherence tomography disclosed vitreoretinal traction release and macular hole closure. No complications were related to the procedure. CONCLUSION: This simple procedure can assist a complete posterior vitreous detachment with relief of the hyaloid-foveolar traction, facilitating macular hole closure.

Transretinal feeder vessel ligature in von Hippel-Lindau disease.

PURPOSE: To present a new technique called transretinal feeder vessel ligature for the treatment of retinal angiomas. METHODS: Case report of a patient with peripheral retinal angiomas previously treated unsuccessfully with photocoagulation who responded to this new, alternative surgical treatment. RESULTS: The retinal angiomas decreased in size although two new feeder vessels appeared and the lesions showed a regression pattern after additional laser therapy over the vascular tumors. CONCLUSIONS: A transretinal feeder vessel ligature in association with vitrectomy and photocoagulation may be useful for some advanced or non-responsive cases of retinal angiomas.

Photodynamic therapy with indocyanine green for occult subfoveal choroidal neovascularization caused by age-related macular degeneration.

PURPOSE: To report two cases of occult subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) that were successfully treated utilizing large spot, low irradiance 810-nm light and intravenous injection of small-volume, high-concentration indocyanine green (ICG) bolus, termed ICG-mediated photodynamic therapy (i-PDT). METHODS: Case report. Two patients with occult subfoveal CNV (two eyes) due to AMD were treated with i-PDT and were prospectively followed with fluorescein and indocyanine green angiography as well as optical coherence tomography (OCT). RESULTS: Both patients presented a 3-line increase in visual acuity by twelve months of follow-up. A significant regression of the CNV was demonstrated by fluorescein angiography within one week following treatment. OCT revealed diminishing of the subretinal fluid. There were no complications related to the procedure. CONCLUSION: i-PDT induced CNV regression and improved the visual acuity in these particular cases, suggesting a new and promising way to treat neovascular AMD. The partial anatomical restoration associated to the improvement of the visual function observed in both patients suggests that a selective therapeutic effect was achieved. Further studies are required not only to assess the clinical value of this treatment but also to better understand the major mechanism of action involving this novel treatment modality.

The feasibility of introducing a visual screening test for children during vaccination campaigns.

PURPOSE: A visual screening test for children was prepared for the use of paramedics during vaccination campaigns. This test was used in a vaccination campaign in Taquaritinga, São Paulo, Brazil. METHODS: The campaign was carried out by two paramedics trained by ophthalmologists. The first 130 children vaccinated whose families showed interest in participating in the visual screening program were chosen. The program consisted of demographic information and eight questions, a visual screening test for children >4 years, and an external eye examination. After studying the data collected, the paramedic decided if the child needed a more thorough ophthalmologic examination. RESULTS: Of the 4505 children vaccinated, 130 children participated in the screening test. One (76.9%) hundred of the 130 children were reexamined by ophthalmologists. Of these, 38 (29.2%) were initially considered to have visual disorders. Ophthalmologic disorders were confirmed in 22 (57.9%) children; of these, 3 were already under ophthalmologic care. The paramedics correctly screened a total of 77 (77%) children. CONCLUSION: Visual screening during vaccination campaigns is simple and rapid, and provides the opportunity to identify children with visual disorders during the critical stage of visual development without the need of ophthalmologists.

Retinal pigment epithelial cells are heterogeneous in their expression of MHC-II after stimulation with interferon-gamma.

The pattern of interferon-gamma-induced major histocompatibility complex Class II antigen expression was evaluated on the retinal pigment epithelium. Experiments were performed in vitro using explant cultures of aged and fetal human eyes and in vivo in albino rabbits. The human explants were stimulated with 50 U ml-1 interferon-gamma for 3 days prior to immunostaining for Class II. The rabbit eyes were subretinally injected in vivo with 50 microl of interferon-gamma (500 U ml-1) and analyzed immunohistochemically 3 days later. A heterogeneous pattern of Class II expression was present in the interferon-gamma-stimulated retinal pigment epithelial cells, in both the in vivo and the in vitro experiments. In aged human eyes the percent of Class-II positive cells was higher in the periphery than in the posterior pole (macular region) after interferon-gamma stimulation (P<0.01). No such difference was found in the fetal eyes. These data demonstrate that retinal pigment epithelial cells are heterogeneous in their response to interferon-gamma. The results are supportive of previous studies demonstrating the structural and proliferative heterogeneity of the retinal pigment epithelium. Together, these studies provide support for the possibility of functional retinal pigment epithelial heterogeneity.

An improved surgical technique for pterygium excision with intraoperative application of mitomycin-C.

A surgical technique was designed to improve safety after pterygium excision with intraoperative application of mitomycin-C (MMC). A limbic incision was performed in 40 eyes. The body of the pterygium was dissected from the episclera to allow its excision. Care was taken to avoid excessive delamination and cauterization of tissues. A 0.02% MMC solution was then applied. Only at the end of the surgery was the head of the pterygium dissected from the cornea. The 8-0 absorbable sutures were used to place both edges of the conjunctiva together to completely cover the area of bare sclera. After a mean follow-up time of 12 months, a recurrence rate of 5% was observed. No complications of therapy were observed. This is a logical alternative to other surgical techniques. However, randomized studies with more patients and longer follow-up are necessary to determine the potential of this procedure in improving the safety of pterygium excision with intraoperative MMC.

Post-traumatic proliferative vitreoretinopathy. The epidemiologic profile, onset, risk factors, and visual outcome.

PURPOSE: The purpose of the study was to characterize the clinical development of proliferative vitreoretinopathy (PVR) after trauma in the human eye. METHODS: A chart review was performed on the records of 1564 patients with ocular trauma seen at a large metropolitan hospital. The frequency, type of ocular trauma, time to onset, potential risk factors, and visual outcome for PVR were evaluated. RESULTS: Proliferative vitreoretinopathy occurred in 71 (4%) of 1654 injured eyes. Of these 71 injured eyes, 30 (42%) resulted from rupture, 15 (21%) from penetration, 13 (18%) from perforation, and 7 (10%) from confusion. Six (9%) were associated with an intraocular foreign body (IOFB). The frequency of PVR following perforation, rupture, penetration, IOFB, and contusion was 43%, 21%, 15%, 11%, and 1%, respectively. Overall, those eyes that developed PVR had a poorer visual outcome, with PVR being the primary reason for visual loss. The time from injury to onset of PVR was shortest after perforation (median, 1.3 months), followed by rupture (2.1 months), IOFB (3.1 months), penetration (3.2 months), and contusion (5.7 months). Vitreous hemorrhage was the strongest independent predictive factor for the development of PVR. A long, posteriorly located wound and persistent intraocular inflammation were also important risk factors for PVR. CONCLUSIONS: These results suggest that PVR is a common complication following a variety of ocular injuries, and that it is associated with a poor visual outcome. Its frequency, onset, and outcome are strongly dependent on the nature of the trauma. Specific high-risk groups are identified as candidates for more aggressive therapy.

A system for classifying mechanical injuries of the eye (globe). The Ocular Trauma Classification Group.

PURPOSE: To develop a classification system for mechanical injuries of the eye. METHODS: The Ocular Trauma Classification Group, a committee of 13 ophthalmologists from seven separate institutions, was organized to discuss the standardization of ocular trauma classification. To develop the classification system, the group reviewed trauma classification systems in ophthalmology and general medicine and, in detail, reports on the characteristics and outcomes of eye trauma, then established a classification system based on standard terminology and features of eye injuries at initial examination that have demonstrated prognostic significance. RESULTS: This system classifies both open-globe and closed-globe injuries according to four separate variables: type of injury, based on the mechanism of injury; grade of injury, defined by visual acuity in the injured eye at initial examination; pupil, defined as the presence or absence of a relative afferent pupillary defect in the injured eye; and zone of injury, based on the anteroposterior extent of the injury. This system is designed to be used by ophthalmologists and nonophthalmologists who care for patients or conduct research on ocular injuries. An ocular injury is classified during the initial examination or at the time of the primary surgical intervention and does not require extraordinary testing. CONCLUSIONS: This classification system will categorize ocular injuries at the time of initial examination. It is designed to promote the use of standard terminology and assessment, with applications to clinical management and research stud ies regarding eye injuries.

Retrovirus-mediated suicide gene transduction in the vitreous cavity of the eye: feasibility in prevention of proliferative vitreoretinopathy.

In proliferative vitreoretinopathy (PVR), retinal pigment epithelial cells, fibroblasts, or other proliferating cells form contractile membranes in the vitreous cavity of the eye, resulting in traction retinal detachment. Retroviral vector-mediated transfer is a suitable method to transduce the herpes simplex virus thymidine kinase (HSV-tk) gene into proliferating cells in PVR, allowing for the selective killing of these cells. To determine the potential of gene transduction in the environment of the vitreous cavity, we evaluated the effect of vitreous humor on retroviral vector-mediated gene transduction of rabbit dermal fibroblasts in vitro and studied in vivo transduction in rabbit experimental PVR with retroviral vector G1BgSvNa. In addition, we studied the bystander effect in vitro and in vivo in a rabbit model of PVR, with low percentages of HSV-tk-positive cells. Finally, we evaluated the efficacy of intravitreal administration of HSV-tk retroviral vector G1TkSvNa followed by ganciclovir (GCV) in the prevention of experimental PVR. Vitreous humor reduced gene transfer efficiency in vitro in a dose-dependent manner. LacZ expression was found in cells of preretinal or intravitreal membranes of animals of both in vivo and in vitro transduction groups; however, in vivo transduction resulted in a decreased number of transduced cells, with a relative transduction efficiency of approximately 2%. Transduction of HSV-tk was associated with a powerful bystander effect both in vitro and in vivo with significant effects even when HSV-tk-positive cells represented only 1% of the population. In vivo transduction with G1TkSvNa followed by GCV significantly inhibited the development of PVR (p < 0.05). These results suggest that retroviral vector-mediated transfer of HSV-tk into the proliferating cells in PVR may be feasible and may provide a novel therapeutic strategy for this disease.

Single intraoperative application versus postoperative mitomycin C eye drops in pterygium surgery.

PURPOSE: To determine the minimum effective dosage, most effective route of administration and long-term effects of mitomycin C for prevention of recurrence after pterygium surgery. METHODS: In a prospective, masked study, 227 patients undergoing surgery for primary pterygia were assigned randomly to five groups: group 1 received a single intraoperative application of 0.2 mg/ml mitomycin C for 3 minutes; group 2 received a single intraoperative application of 0.4 mg/ml mitomycin C for 3 minutes; group 3 received mitomycin C eye drops 0.2 mg/ml three times daily for 7 days; group 4 received mitomycin C eye drops 0.4 mg/ml three times daily for 14 days; group 5 acted as a control (surgery alone). RESULTS: After a mean follow-up time of 28 months, recurrence rates of 6.66%, 4.08%, 4.26%, 4.44%, and 29.27%, respectively, were observed. Statistical analysis showed significant differences between groups receiving mitomycin C and the control (P < or = 0.001). There was no statistical difference among treated groups (P > or = 0.0681). No complications of therapy were observed. CONCLUSION: These results support the efficacy and relative safety of a single, low-concentration, intraoperative application of mitomycin C in pterygium surgery together with the use of a conjunctival flap, avoiding excessive cauterization of the sclera and leaving bare sclera.